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研究生:謝郁平
研究生(外文):Yu-Ping Hsieh
論文名稱:EGCG抑制檳榔鹼Arecoline經由TGF-β1訊息傳遞路徑誘導人類頰黏膜纖維母細胞及上皮細胞早期生長反應因子表現之研究
論文名稱(外文):Arecoline induced Egr-1 synthesis via TGF-β1 signaling pathway in human buccal fibroblasts and epithelial cells: inhibition by EGCG
指導教授:陳信銘陳信銘引用關係郭彥彬郭彥彬引用關係
指導教授(外文):Hsin-Ming ChenMark Yen-Ping Kuo
口試委員:張國威張育超張正琪
口試委員(外文):Kuo-Wei ChangYu-Chao ChangCheng-Chi Chang
口試日期:2016-07-26
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:臨床牙醫學研究所
學門:醫藥衛生學門
學類:牙醫學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:139
中文關鍵詞:口腔黏膜下纖維化症(OSF)檳榔鹼(Arecoline)早期生長反應因子(Egr-1)兒茶素(EGCG)活性氧化物(ROS)粒線體超氧化物(mitochondrial superoxide)潛在的轉化生長因子(latent TGF-β1)肌纖維母細胞分化(myofibroblast differentiation)上皮-間質細胞轉化(EMT)
外文關鍵詞:Oral submucous fibrosis(OSF)ArecolineEarly growth response-1(Egr-1)EGCGReactive oxygen species(ROS)mitochondrial superoxidelatent Transforming growth factor-β1(latent TGF-β1)myofibroblast differentiationEpithelial-mesenchymal transition(EMT)
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嚼食檳榔是造成口腔黏膜下纖維化症(Oral submucous fibrosis,OSF)的最主要原因。文獻指出檳榔中的主要成分檳榔鹼(Arecoline)會誘導許多纖維化相關基因的表現。早期生長反應因子(Early growth response-1,Egr-1)是一個轉錄因子,研究發現Egr-1的表現與纖維化疾病呈現高度正相關性,但Egr-1在OSF中扮演角色並不清楚。本研究首先利用免疫組織化學染色方法,發現在正常口腔黏膜(NOM)中,其上皮細胞並沒有Egr-1的表現,在頰黏膜纖維母細胞(buccal mucosal fibroblast,BMF)及發炎細胞的細胞質與細胞核中,則有發現些微的Egr-1表現。在OSF組織切片中,其上皮細胞、BMF細胞及發炎細胞的細胞質與細胞核皆有Egr-1的陽性濃染。接著我們發現Arecoline會誘導BMF細胞中Egr-1的表現,而Src抑制劑、ERK抑制劑、JNK抑制劑以及抗氧化劑NAC能夠明顯降低Arecoline誘導BMF細胞中Egr-1的表現。此外,我們發現兒茶素(EGCG)對於Arecoline誘導BMF細胞中Egr-1的表現、collagen的合成以及肌纖維母細胞的分化皆有明顯的抑制效果。此外,Src抑制劑、ERK抑制劑、JNK抑制劑、ALK5抑制劑、Smad3抑制劑以及Smad3 siRNA能夠明顯降低TGF-β1誘導BMF細胞中Egr-1的表現。Egr-1 siRNA可以明顯抑制TGF-β1誘導BMF細胞collagen的合成以及肌纖維母細胞的分化。此外,EGCG可以抑制TGF-β1誘導BMF細胞中Egr-1的表現、collagen的合成以及肌纖維母細胞的分化。進一步發現TGF-β1會誘導BMF細胞中NADPH oxidase 4(NOX4)的表現,而抗氧化劑NAC,NOX family抑制劑以及NOX4抑制劑能夠抑制TGF-β1誘導BMF細胞中Egr-1的表現及ROS的產生。抗氧化劑NAC能夠抑制TGF-β1誘導BMF細胞中Src的磷酸化,NOX4抑制劑、Src抑制劑及NOX4 siRNA可以有效抑制TGF-β1誘導BMF細胞中Src、ERK、JNK及Smad3的磷酸化,顯示NOX4/ROS位於Src上游且Src位於ERK、JNK及Smad3的上游。我們使用TGF-β中和抗體、ALK5抑制劑以及Smad3抑制劑發現可有效降低Arecoline誘導BMF細胞中Egr-1的表現、膠原蛋白的合成以及肌纖維母細胞的分化,顯示Arecoline會開啟TGF-β訊息傳遞路徑。進一步發現Arecoline可以增加BMF細胞培養液中活化態TGF-β1的表現量。前處理抗氧化劑NAC及GSH能夠明顯降低Arecoline誘導BMF細胞的活化態TGF-β1。抗氧化劑NAC及Trolox,PEG-catalase,mitochondria-targeted O2-抑制劑以及MnTBAP能夠明顯抑制Arecoline誘導BMF細胞活化態TGF-β1的表現量。直接加入H2O2會誘導BMF細胞活化態TGF-β1的表現,且mitochondria-targeted O2-抑制劑可以明顯降低Arecoline誘導BMF細胞mitochondrial superoxide的產生。這些結果顯示Arecoline是經由粒線體來源的Superoxide(O2-)及H2O2來誘導BMF細胞活化TGF-β1。EGCG可抑制Arecoline誘導BMF細胞mitochondrial superoxide的產生以及TGF-β1的活化。過去研究發現,口腔上皮細胞受到TGF-β刺激會產生上皮-間質細胞轉化 (Epithelium-mesenchymal transition,EMT),在OSF的進程中扮演重要角色。我們選用頰黏膜上皮細胞株TW2.6細胞來探討Egr-1是否扮演調控EMT的角色。我們發現TGF-β1會誘導TW2.6細胞中Egr-1及Vimentin的表現,並降低E-cadherin的表現。使用Egr-1 siRNA可以明顯抑制TGF-β1誘導TW2.6細胞中Egr-1及Snail的表現,並且回復EMT的現象。我們發現Src抑制劑、JNK抑制劑、抗氧化劑NAC、NOX family抑制劑、NOX4抑制劑、ALK5抑制劑以及Smad3抑制劑皆可明顯抑制TGF-β1誘導TW2.6細胞中Egr-1及Snail的表現。我們還發現EGCG可以明顯抑制TGF-β1誘導TW2.6細胞中Egr-1及Snail的表現,並且回復EMT的現象。這些結果顯示EGCG對於預防或治療OSF具有極大的潛力。

Areca nut (AN) chewing is the most important risk factor of oral submucous fibrosis (OSF). Early growth response-1 (Egr-1) protein has been shown to play a central role in the pathogenesis of many human fibrotic diseases. We immunohistochemically examined the expression of Egr-1 protein in OSF specimens. Positive Egr-1 staining was detected in subepithelial fibroblasts and inflammatory cells. We further observed Arecoline, a main alkaloid found in AN, increased Egr-1 synthesis in a dose- and time- dependent manner in buccal mucosal fibroblasts. Constitutive overexpression of Egr-1 during AN chewing may play a role in the pathogenesis of OSF. Pretreatment with antioxidant NAC, JNK inhibitor and ERK inhibitor significantly reduced Arecoline induced Egr-1 synthesis. Furthermore, epigallocatechin-3-gallate (EGCG) completely inhibited Arecoline-induced Egr-1 synthesis and the inhibition is dose-dependent. Transforming growth factor β (TGF-β) is a key regulator in the pathogenesis of OSF. Egr-1 is an important mediator of TGF-β-induced responses and is considered to play a central role in orchestrating fibrotic responses. Egr-1 may contribute to the pathogenesis of OSF as it is overexpressed in OSF specimens and in Arecoline-stimulated normal human buccal mucosal fibroblasts (BMFs). Previous study has shown that the stimulation of Egr-1 by TGF- in dermal fibroblasts occurs independent of the activin receptor-like kinase 5 (ALK5)/Smad3 signaling axis. Since Egr-1 is essential for the fibrotic response to TGF- and that TGF- signaling is cell type-and context-dependent, we aimed to examine the possible signal transduction pathways involved in TGF-β1-induced Egr-1 expression in BMFs. In the present study, we have shown that TGF-β1 induces Egr-1 expression and that Egr-1 mediates the TGF-β1-induced mRNAs expression of the α1- and α2-chains of type I collagen (COL1A1 and COL1A2) and the acid-soluble collagen production in BMFs. We have also shown that ALK5 inhibitor, ERK inhibitor, JNK inhibitor, and Smad3 inhibitor significantly abrogate the TGF-β1-induced levels of Egr-1 protein, indicating that ALK5/Smad3, ERK, and JNK are involved in the TGF-β1-induced Egr-1 in BMFs. We have further demonstrated that knocking down Smad3 using Smad2/3 siRNA completely abolishes the TGF1-induced Egr-1. Moreover, EGCG fully inhibits TGF-β1-induced Egr-1 expression and abrogates the TGF-1-stimulated production of acid-soluble collagens. We found TGF-β1 induced NADPH oxidase 4 (NOX4) expression in BMFs. Pretreatment with antioxidant NAC, NOX family inhibitor, and NOX4 inhibitor significantly reduced TGF-β1-induced Egr-1 expression and ROS production in BMFs. We found antioxidant NAC significantly inhibited TGF-β1-induced Src phosphorylation in BMFs. In addition, NOX4 inhibitor, Src inhibitor, and NOX4 siRNA significantly inhibited TGF-β1-induced Src, ERK, JNK, and Smad3 phosphorylation in BMFs. These results showed that TGF-β1-induced Src phosphorylation is regulated by NOX4/ROS, and Src is an upstream signaling transducer of ERK, JNK, and Smad3 in BMFs. We found Arecoline increased activated TGF-β1 level in BMFs. Pretreatment with antioxidant NAC and GSH significantly reduced Arecoline-induced activated TGF-β1 level in BMFs. We further found antioxidant NAC and Trolox, PEG-catalase, mitochondria-targeted O2- inhibitor, and MnTBAP significantly inhibited Arecoline-induced activated TGF-β1 level in BMFs. We found H2O2 increased activated TGF-β1 level in BMFs. Mitochondria-targeted O2- inhibitor significantly reduced Arecoline-induced mitochondrial superoxide in BMFs. These results showed that Arecoline increased activated TGF-β1 level via mitochondrial superoxide and H2O2 in BMFs. We further found EGCG significantly inhibited Arecoline-induced mitochondrial superoxide and activated TGF-β1 level in BMFs. Epithelial-mesenchymal transition (EMT) is a big issue in fibrosis disease. We investigate whether Egr-1 play a role in regulating EMT in TW2.6 cells. We found TGF-β1 induced Egr-1 and Vimentin expression and reduced E-cadherin expression in TW2.6 cells. Genetic targeting of Egr-1 by Egr-1 siRNA significantly inhibited TGF-β1-induced Egr-1 and Snail expression and reduced TGF-β1-induced EMT in TW2.6 cells. We found Src inhibitor, JNK inhibitor, antioxidant NAC, NOX family inhibitor, NOX4 inhibitor, ALK5 inhibitor, and Smad3 inhibitor significantly inhibited TGF-β1-induced Egr-1 and Snail expression in TW2.6 cells. We further found EGCG significantly inhibited TGF-β1-induced Egr-1 and Snail expression and reduced TGF-β1-induced EMT in TW2.6 cells. EGCG potentially qualifies as a useful reagent for the prevention and therapy of OSF.

口試委員會審定書…………………………………………………………………….Ⅰ
謝誌…………………………………………………………………………………….Ⅱ
中文摘要………………………………………………………………………….……Ⅲ
Abstract…………………………………………………………………………………Ⅴ
第一章 導論…………………………………………………………………………….1
第一節 口腔黏膜下纖維化(Oral submucous fibrosis,OSF)…………………….1
1-1 OSF的簡介……………………………………………………………….1
1-2 OSF的流行病學………………………………………………………….1
1-3 OSF的致病機轉………………………………………………………….2
1-4 OSF的治療………………………………………………………………4
第二節 檳榔鹼(Arecoline)……………………………………………………….5
2-1 Arecoline的訊息傳遞路徑……………………………………………….5
2-2 Arecoline與纖維化……………………………………………………….6
第三節 轉化生長因子(Transforming growth factor-β1,TGF-β1)……………….8
3-1 TGF-β1的簡介……………………………………………………………8
3-2 TGF-β1的訊息傳遞路徑…………………………………………………9
3-3 TGF-β1與纖維化………………………………………………………..11
第四節 早期生長反應因子(Early growth response-1,Egr-1)………………….13
4-1 Egr-1的簡介…………………………………………………………….13
4-2 Egr-1與纖維化………………………………………………………….14
4-3 Egr-1與EMT……………………………………………………………15
第五節 活性氧化物(Reactive oxygen species,ROS)…………………………..16
5-1 ROS的簡介……………………………………………………………...16
5-2 ROS與纖維化…………………………………………………………...17
5-3 NOX4與纖維化…………………………………………………………18
5-4 Mitochondrial superoxide與纖維化……………………………………19
第六節 兒茶素(Epigallocatechin-3-gallate,EGCG)……………………………20
第二章 實驗目的……………………………………………………………………...22
第三章 材料與方法…………………………………………………………………...23
第一節 檢體收集………………………………………………………………...23
第二節 免疫組織化學染色(Immunohistochemistry,IHC)…………………….24
第三節 細胞株與細胞培養……………………………………………………...27
第四節 藥物處理………………………………………………………………...29
第五節 西方墨點法(Western blot)……………………………………………...33
第六節 定量即時聚合酶鏈鎖反應(Quantitative real-time polymerase chain reaction,qPCR)………………………………………………………...36
第七節 Sircol collagen assay……………………………………………………38
第八節 Collagen gel contraction assay…………………………………………39
第九節 siRNA transfection……………………………………………………...40
第十節 流式細胞儀檢測細胞ROS含量………………………………………..41
第十一節 Enzyme-linked immunosorbent assay(ELISA)…………………….43
第十二節 統計分析……………………………………………………………...45
第四章 結果…………………………………………………………………………...46
第一節 EGCG抑制Arecoline誘導BMF細胞Egr-1、collagen表現以及collagen gel contraction…………………………………………………………...46
第二節 EGCG經由抑制Egr-1而降低TGF-β1誘導BMF細胞collagen表現以及collagen gel contraction……………………………………………...49
第三節 TGF-β1經由NOX4/ROS/Src/ERK、JNK、Smad3誘導BMF細胞Egr-1、collagen表現以及collagen gel contraction……………………………53
第四節 Arecoline經由mitochondrial ROS誘導BMF細胞釋出活化態TGF-β1…………………………………………………………………..55
第五節 TGF-β1經由NOX4/ROS/Src/ JNK、Smad3誘導TW2.6細胞Egr-1及EMT相關蛋白質的表現………………………………………………..58
第五章 討論…………………………………………………………………………...61
第六章 圖與表………………………………………………………………………...66
第七章 References…………………………………………………………………...95
附錄一………………………………………………………………………………...128
附錄二………………………………………………………………………………...133


Aggeli IK, Beis I, Gaitanaki C (2010). ERKs and JNKs mediate hydrogen peroxide-induced Egr-1 expression and nuclear accumulation in H9c2 cells. Physiol Res 59(3):443-454.

Aitken RJ, Roman SD (2008). Antioxidant systems and oxidative stress in the testes. Oxid Med Cell Longev 1(1):15-24.

Allen JT, Knight RA, Bloor CA, Spiteri MA (1999). Enhanced insulin-like growth factor binding protein-related protein 2 (Connective tissue growth factor) expression in patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Cell Mol Biol 21(6):693-700.

Altenhofer S, Kleikers PW, Radermacher KA, Scheurer P, Rob Hermans JJ, Schiffers P et al. (2012). The NOX toolbox: validating the role of NADPH oxidases in physiology and disease. Cell Mol Life Sci 69(14):2327-2343.

Angadi PV, Rao SS (2011). Areca nut in pathogenesis of oral submucous fibrosis: revisited. Oral Maxillofac Surg 15(1):1-9.

Annes JP, Munger JS, Rifkin DB (2003). Making sense of latent TGFbeta activation. J Cell Sci 116(Pt 2):217-224.

Auluck A, Rosin MP, Zhang L, Sumanth KN (2008). Oral submucous fibrosis, a clinically benign but potentially malignant disease: report of 3 cases and review of the literature. J Can Dent Assoc 74(8):735-740.

Baron V, Adamson ED, Calogero A, Ragona G, Mercola D (2006). The transcription factor Egr1 is a direct regulator of multiple tumor suppressors including TGFbeta1, PTEN, p53, and fibronectin. Cancer Gene Ther 13(2):115-124.

Bhattacharyya S, Chen SJ, Wu M, Warner-Blankenship M, Ning H, Lakos G et al. (2008). Smad-independent transforming growth factor-beta regulation of early growth response-1 and sustained expression in fibrosis: implications for scleroderma. Am J Pathol 173(4):1085-1099.

Bhattacharyya S, Wu M, Fang F, Tourtellotte W, Feghali-Bostwick C, Varga J (2011). Early growth response transcription factors: key mediators of fibrosis and novel targets for anti-fibrotic therapy. Matrix Biol 30(4):235-242.

Bhattacharyya S, Fang F, Tourtellotte W, Varga J (2013). Egr-1: new conductor for the tissue repair orchestra directs harmony (regeneration) or cacophony (fibrosis). J Pathol 229(2):286-297.

Bishen KA, Radhakrishnan R, Satyamoorthy K (2008). The role of basic fibroblast growth factor in oral submucous fibrosis pathogenesis. J Oral Pathol Med 37(7):402-411.

Black SA, Jr., Palamakumbura AH, Stan M, Trackman PC (2007). Tissue-specific mechanisms for CCN2/CTGF persistence in fibrotic gingiva: interactions between cAMP and MAPK signaling pathways, and prostaglandin E2-EP3 receptor mediated activation of the c-JUN N-terminal kinase. J Biol Chem 282(21):15416-15429.

Black SA, Jr., Trackman PC (2008). Transforming growth factor-beta1 (TGFbeta1) stimulates connective tissue growth factor (CCN2/CTGF) expression in human gingival fibroblasts through a RhoA-independent, Rac1/Cdc42-dependent mechanism: statins with forskolin block TGFbeta1-induced CCN2/CTGF expression. J Biol Chem 283(16):10835-10847.

Blobe GC, Schiemann WP, Lodish HF (2000). Role of transforming growth factor beta in human disease. N Engl J Med 342(18):1350-1358.

Bonniaud P, Margetts PJ, Kolb M, Schroeder JA, Kapoun AM, Damm D et al. (2005). Progressive transforming growth factor beta1-induced lung fibrosis is blocked by an orally active ALK5 kinase inhibitor. Am J Respir Crit Care Med 171(8):889-898.

Breitkopf K, Haas S, Wiercinska E, Singer MV, Dooley S (2005). Anti-TGF-beta strategies for the treatment of chronic liver disease. Alcohol Clin Exp Res 29(11 Suppl):121S-131S.

Buduneli N, Kutukculer N, Aksu G, Atilla G (2001). Evaluation of transforming growth factor-beta 1 level in crevicular fluid of cyclosporin A-treated patients. J Periodontol 72(4):526-531.

Cai Y, Yu SS, Chen TT, Gao S, Geng B, Yu Y et al. (2013). EGCG inhibits CTGF expression via blocking NF-kappaB activation in cardiac fibroblast. Phytomedicine 20(2):106-113.

Canniff JP, Harvey W (1981). The aetiology of oral submucous fibrosis: the stimulation of collagen synthesis by extracts of areca nut. Int J Oral Surg 10(Suppl 1):163-167.

Chang JZ, Yang WH, Deng YT, Chen HM, Kuo MY (2012). Thrombin-stimulated connective tissue growth factor (CTGF/CCN2) production in human buccal mucosal fibroblasts: Inhibition by epigallocatechin-3-gallate. Head Neck 34(8):1089-1094.

Chang JZ, Yang WH, Deng YT, Chen HM, Kuo MY (2013). EGCG blocks TGFbeta1-induced CCN2 by suppressing JNK and p38 in buccal fibroblasts. Clin Oral Investig 17(2):455-461.

Chang MC, Chan CP, Chen YJ, Hsien HC, Chang YC, Yeung SY et al. (2016). Areca nut components stimulate ADAM17, IL-1alpha, PGE2 and 8-isoprostane production in oral keratinocyte: role of reactive oxygen species, EGF and JAK signaling. Oncotarget 7(13):16879-16894.

Chang Y, Wu XY (2010). JNK1/2 siRNA inhibits transforming-growth factor-beta1-induced connective tissue growth factor expression and fibrotic function in THSFs. Mol Cell Biochem 335(1-2):83-89.

Chang YC, Tai KW, Cheng MH, Chou LS, Chou MY (1998). Cytotoxic and non-genotoxic effects of arecoline on human buccal fibroblasts in vitro. J Oral Pathol Med 27(2):68-71.

Chang YC, Yang SF, Tai KW, Chou MY, Hsieh YS (2002). Increased tissue inhibitor of metalloproteinase-1 expression and inhibition of gelatinase A activity in buccal mucosal fibroblasts by arecoline as possible mechanisms for oral submucous fibrosis. Oral Oncol 38(2):195-200.

Chen D, Milacic V, Chen MS, Wan SB, Lam WH, Huo C et al. (2008). Tea polyphenols, their biological effects and potential molecular targets. Histol Histopathol 23(4):487-496.

Chen HM, Hsieh RP, Yang H, Kuo YS, Kuo MY, Chiang CP (2004). HLA typing in Taiwanese patients with oral submucous fibrosis. J Oral Pathol Med 33(4):191-199.

Chen N, Bezzina R, Hinch E, Lewandowski PA, Cameron-Smith D, Mathai ML et al. (2009). Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet. Nutr Res 29(11):784-793.

Chen SJ, Ning H, Ishida W, Sodin-Semrl S, Takagawa S, Mori Y et al. (2006). The early-immediate gene EGR-1 is induced by transforming growth factor-beta and mediates stimulation of collagen gene expression. J Biol Chem 281(30):21183-21197.

Cheng HL, Su SJ, Huang LW, Hsieh BS, Hu YC, Hung TC et al. (2010). Arecoline induces HA22T/VGH hepatoma cells to undergo anoikis - involvement of STAT3 and RhoA activation. Mol Cancer 9(126.

Cheng JC, Chang HM, Leung PC (2013). Egr-1 mediates epidermal growth factor-induced downregulation of E-cadherin expression via Slug in human ovarian cancer cells. Oncogene 32(8):1041-1049.

Chiang CP, Hsieh RP, Chen TH, Chang YF, Liu BY, Wang JT et al. (2002). High incidence of autoantibodies in Taiwanese patients with oral submucous fibrosis. J Oral Pathol Med 31(7):402-409.

Chu L, Wang T, Hu Y, Gu Y, Su Z, Jiang H (2013). Activation of Egr-1 in human lung epithelial cells exposed to silica through MAPKs signaling pathways. PLoS One 8(7):e68943.

Chung-Hung T, Shun-Fa Y, Yu-Chao C (2007). The upregulation of cystatin C in oral submucous fibrosis. Oral Oncol 43(7):680-685.

Coletta RD, Graner E (2006). Hereditary gingival fibromatosis: a systematic review. J Periodontol 77(5):753-764.

Cox SC, Walker DM (1997). Establishing a normal range for mouth opening: its use in screening for oral submucous fibrosis. Br J Oral Maxillofac Surg 35(1):40-42.

D''Autreaux B, Toledano MB (2007). ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nat Rev Mol Cell Biol 8(10):813-824.

de Gouville AC, Boullay V, Krysa G, Pilot J, Brusq JM, Loriolle F et al. (2005). Inhibition of TGF-beta signaling by an ALK5 inhibitor protects rats from dimethylnitrosamine-induced liver fibrosis. Br J Pharmacol 145(2):166-177.

de Mejia EG, Ramirez-Mares MV, Puangpraphant S (2009). Bioactive components of tea: cancer, inflammation and behavior. Brain Behav Immun 23(6):721-731.

Deng YT, Chen HM, Cheng SJ, Chiang CP, Kuo MY (2009). Arecoline-stimulated connective tissue growth factor production in human buccal mucosal fibroblasts: Modulation by curcumin. Oral Oncol 45(9):e99-e105.

Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hsu VM et al. (2007). Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum 56(1):323-333.

Devika PT, Stanely Mainzen Prince P (2009). Preventive effect of (-)epigallocatechin gallate on lipids, lipoproteins, and enzymes of lipid metabolism in isoproterenol-induced myocardial infarction in rats. J Biochem Mol Toxicol 23(6):387-393.

Dietz HC (2015). One integrin to rule them all? Sci Transl Med 7(288):288fs221.

Droge W (2002). Free radicals in the physiological control of cell function. Physiol Rev 82(1):47-95.

Eldred JA, Hodgkinson LM, Dawes LJ, Reddan JR, Edwards DR, Wormstone IM (2012). MMP2 activity is critical for TGFbeta2-induced matrix contraction--implications for fibrosis. Invest Ophthalmol Vis Sci 53(7):4085-4098.

Flanders KC, Sullivan CD, Fujii M, Sowers A, Anzano MA, Arabshahi A et al. (2002). Mice lacking Smad3 are protected against cutaneous injury induced by ionizing radiation. Am J Pathol 160(3):1057-1068.

Flanders KC (2004). Smad3 as a mediator of the fibrotic response. Int J Exp Pathol 85(2):47-64.

Fortunel NO, Hatzfeld A, Hatzfeld JA (2000). Transforming growth factor-beta: pleiotropic role in the regulation of hematopoiesis. Blood 96(6):2022-2036.

Fu K, Corbley MJ, Sun L, Friedman JE, Shan F, Papadatos JL et al. (2008). SM16, an orally active TGF-beta type I receptor inhibitor prevents myofibroblast induction and vascular fibrosis in the rat carotid injury model. Arterioscler Thromb Vasc Biol 28(4):665-671.

Fukasawa H, Yamamoto T, Suzuki H, Togawa A, Ohashi N, Fujigaki Y et al. (2004). Treatment with anti-TGF-beta antibody ameliorates chronic progressive nephritis by inhibiting Smad/TGF-beta signaling. Kidney Int 65(1):63-74.

Gabrielli A, Avvedimento EV, Krieg T (2009). Scleroderma. N Engl J Med 360(19):1989-2003.

Gaggioli C, Deckert M, Robert G, Abbe P, Batoz M, Ehrengruber MU et al. (2005). HGF induces fibronectin matrix synthesis in melanoma cells through MAP kinase-dependent signaling pathway and induction of Egr-1. Oncogene 24(8):1423-1433.

Gagliardini E, Benigni A (2006). Role of anti-TGF-beta antibodies in the treatment of renal injury. Cytokine Growth Factor Rev 17(1-2):89-96.

Garg K, Corona BT, Walters TJ (2015). Therapeutic strategies for preventing skeletal muscle fibrosis after injury. Front Pharmacol 6(87.

Gashler A, Sukhatme VP (1995). Early growth response protein 1 (Egr-1): prototype of a zinc-finger family of transcription factors. Prog Nucleic Acid Res Mol Biol 50(191-224.

Ghosh AK, Quaggin SE, Vaughan DE (2013). Molecular basis of organ fibrosis: potential therapeutic approaches. Exp Biol Med (Maywood) 238(5):461-481.

Gosslar U, Schmid RM, Holzmann B (1999). Regulation of Egr-1-dependent gene expression by the C-terminal activation domain. Biochem Biophys Res Commun 255(2):208-215.

Grotegut S, von Schweinitz D, Christofori G, Lehembre F (2006). Hepatocyte growth factor induces cell scattering through MAPK/Egr-1-mediated upregulation of Snail. EMBO J 25(15):3534-3545.

Guha M, O''Connell MA, Pawlinski R, Hollis A, McGovern P, Yan SF et al. (2001). Lipopolysaccharide activation of the MEK-ERK1/2 pathway in human monocytic cells mediates tissue factor and tumor necrosis factor alpha expression by inducing Elk-1 phosphorylation and Egr-1 expression. Blood 98(5):1429-1439.

Guo F, Carter DE, Leask A (2011). Mechanical tension increases CCN2/CTGF expression and proliferation in gingival fibroblasts via a TGFbeta-dependent mechanism. PLoS One 6(5):e19756.

Haque MF, Meghji S, Khitab U, Harris M (2000). Oral submucous fibrosis patients have altered levels of cytokine production. J Oral Pathol Med 29(3):123-128.

Hardie J (1987). Oral submucous fibrosis. A review with case reports. J Can Dent Assoc 53(5):389-393.

Harvey W, Scutt A, Meghji S, Canniff JP (1986). Stimulation of human buccal mucosa fibroblasts in vitro by betel-nut alkaloids. Arch Oral Biol 31(1):45-49.

Hasan RN, Schafer AI (2008). Hemin upregulates Egr-1 expression in vascular smooth muscle cells via reactive oxygen species ERK-1/2-Elk-1 and NF-kappaB. Circ Res 102(1):42-50.

Hasegawa R, Chujo T, Sai-Kato K, Umemura T, Tanimura A, Kurokawa Y (1995). Preventive effects of green tea against liver oxidative DNA damage and hepatotoxicity in rats treated with 2-nitropropane. Food Chem Toxicol 33(11):961-970.

Hasegawa T, Nakao A, Sumiyoshi K, Tsuchihashi H, Ogawa H (2005). SB-431542 inhibits TGF-beta-induced contraction of collagen gel by normal and keloid fibroblasts. J Dermatol Sci 39(1):33-38.

Hayashi H, Sakai T (2012). Biological Significance of Local TGF-beta Activation in Liver Diseases. Front Physiol 3(12.

Higashiyama H, Yoshimoto D, Kaise T, Matsubara S, Fujiwara M, Kikkawa H et al. (2007). Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis. Exp Mol Pathol 83(1):39-46.

Higdon JV, Frei B (2003). Tea catechins and polyphenols: health effects, metabolism, and antioxidant functions. Crit Rev Food Sci Nutr 43(1):89-143.

Hjoberg J, Le L, Imrich A, Subramaniam V, Mathew SI, Vallone J et al. (2004). Induction of early growth-response factor 1 by platelet-derived growth factor in human airway smooth muscle. Am J Physiol Lung Cell Mol Physiol 286(4):L817-825.

Holmes A, Abraham DJ, Sa S, Shiwen X, Black CM, Leask A (2001). CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling. J Biol Chem 276(14):10594-10601.

Huang L, Haylor JL, Fisher M, Hau Z, El Nahas AM, Griffin M et al. (2010). Do changes in transglutaminase activity alter latent transforming growth factor beta activation in experimental diabetic nephropathy? Nephrol Dial Transplant 25(12):3897-3910.

Ito Y, Aten J, Bende RJ, Oemar BS, Rabelink TJ, Weening JJ et al. (1998). Expression of connective tissue growth factor in human renal fibrosis. Kidney Int 53(4):853-861.

Iwanaga K, Murata T, Okada M, Hori M, Ozaki H (2009). Carbachol induces Ca(2+)-dependent contraction via muscarinic M2 and M3 receptors in rat intestinal subepithelial myofibroblasts. J Pharmacol Sci 110(3):306-314.

Jeng JH, Kuo ML, Hahn LJ, Kuo MY (1994). Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro. J Dent Res 73(5):1043-1049.

Jeng JH, Lan WH, Hahn LJ, Hsieh CC, Kuo MY (1996). Inhibition of the migration, attachment, spreading, growth and collagen synthesis of human gingival fibroblasts by arecoline, a major areca alkaloid, in vitro. J Oral Pathol Med 25(7):371-375.

Jiang F, Liu GS, Dusting GJ, Chan EC (2014). NADPH oxidase-dependent redox signaling in TGF-beta-mediated fibrotic responses. Redox Biol 2(267-272.

Jing K, Shin S, Jeong S, Kim S, Song KS, Park JH et al. (2014). Docosahexaenoic acid induces the degradation of HPV E6/E7 oncoproteins by activating the ubiquitin-proteasome system. Cell Death Dis 5(e1524.

Kang JS, Liu C, Derynck R (2009). New regulatory mechanisms of TGF-beta receptor function. Trends Cell Biol 19(8):385-394.

Kang JS, Park IH, Cho JS, Hong SM, Kim TH, Lee SH et al. (2014). Epigallocatechin-3-gallate inhibits collagen production of nasal polyp-derived fibroblasts. Phytother Res 28(1):98-103.

Kaufmann K, Thiel G (2002). Epidermal growth factor and thrombin induced proliferation of immortalized human keratinocytes is coupled to the synthesis of Egr-1, a zinc finger transcriptional regulator. J Cell Biochem 85(2):381-391.

Kawai K, Tsuno NH, Kitayama J, Okaji Y, Yazawa K, Asakage M et al. (2003). Epigallocatechin gallate, the main component of tea polyphenol, binds to CD4 and interferes with gp120 binding. J Allergy Clin Immunol 112(5):951-957.

Khachigian LM, Collins T (1998). Early growth response factor 1: a pleiotropic mediator of inducible gene expression. J Mol Med (Berl) 76(9):613-616.

Khachigian LM (2006). Early growth response-1 in cardiovascular pathobiology. Circ Res 98(2):186-191.

Kim SS, Jackson-Boeters L, Darling MR, Rieder MJ, Hamilton DW (2013). Nifedipine induces periostin expression in gingival fibroblasts through TGF-beta. J Dent Res 92(11):1022-1028.

Kok SH, Hong CY, Lin SK, Lee JJ, Chiang CP, Kuo MY (2007). Establishment and characterization of a tumorigenic cell line from areca quid and tobacco smoke-associated buccal carcinoma. Oral Oncol 43(7):639-647.

Koli K, Myllarniemi M, Keski-Oja J, Kinnula VL (2008). Transforming growth factor-beta activation in the lung: focus on fibrosis and reactive oxygen species. Antioxid Redox Signal 10(2):333-342.

Kondo T, Takemura G, Kosai K, Ohno T, Takahashi T, Esaki M et al. (2008). Application of an adenoviral vector encoding soluble transforming growth factor-beta type II receptor to the treatment of diabetic nephropathy in mice. Clin Exp Pharmacol Physiol 35(11):1288-1293.

Kramer EL, Mushaben EM, Pastura PA, Acciani TH, Deutsch GH, Khurana Hershey GK et al. (2009). Early growth response-1 suppresses epidermal growth factor receptor-mediated airway hyperresponsiveness and lung remodeling in mice. Am J Respir Cell Mol Biol 41(4):415-425.

Kumpawat K, Deb S, Ray S, Chatterjee A (2003). Genotoxic effect of raw betel-nut extract in relation to endogenous glutathione levels and its mechanism of action in mammalian cells. Mutat Res 538(1-2):1-12.

Kuo PL, Chen YH, Chen TC, Shen KH, Hsu YL (2011). CXCL5/ENA78 increased cell migration and epithelial-to-mesenchymal transition of hormone-independent prostate cancer by early growth response-1/snail signaling pathway. J Cell Physiol 226(5):1224-1231.

Kuo TM, Luo SY, Chiang SL, Lee CP, Liu YF, Chang JG et al. (2014). Arecoline induces TNF-alpha production and Zonula Occludens-1 redistribution in mouse Sertoli TM4 cells. J Biomed Sci 21(93.

Kuru L, Yilmaz S, Kuru B, Kose KN, Noyan U (2004). Expression of growth factors in the gingival crevice fluid of patients with phenytoin-induced gingival enlargement. Arch Oral Biol 49(11):945-950.

Lai JK, Wu HC, Shen YC, Hsieh HY, Yang SY, Chang CC (2012). Kruppel-like factor 4 is involved in cell scattering induced by hepatocyte growth factor. J Cell Sci 125(Pt 20):4853-4864.

Laskaris G, Bovopoulou O, Nicolis G (1981). Oral submucous fibrosis in a Greek female. Br J Oral Surg 19(3):197-201.

Latella G, Vetuschi A, Sferra R, Zanninelli G, D''Angelo A, Catitti V et al. (2009). Smad3 loss confers resistance to the development of trinitrobenzene sulfonic acid-induced colorectal fibrosis. Eur J Clin Invest 39(2):145-156.

Leask A, Sa S, Holmes A, Shiwen X, Black CM, Abraham DJ (2001). The control of ccn2 (ctgf) gene expression in normal and scleroderma fibroblasts. Mol Pathol 54(3):180-183.

Leask A, Holmes A, Black CM, Abraham DJ (2003). Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts. J Biol Chem 278(15):13008-13015.

Leask A, Abraham DJ (2004). TGF-beta signaling and the fibrotic response. FASEB J 18(7):816-827.

Leivonen SK, Chantry A, Hakkinen L, Han J, Kahari VM (2002). Smad3 mediates transforming growth factor-beta-induced collagenase-3 (matrix metalloproteinase-13) expression in human gingival fibroblasts. Evidence for cross-talk between Smad3 and p38 signaling pathways. J Biol Chem 277(48):46338-46346.

Leivonen SK, Hakkinen L, Liu D, Kahari VM (2005). Smad3 and extracellular signal-regulated kinase 1/2 coordinately mediate transforming growth factor-beta-induced expression of connective tissue growth factor in human fibroblasts. J Invest Dermatol 124(6):1162-1169.

Li CJ, Ning W, Matthay MA, Feghali-Bostwick CA, Choi AM (2007). MAPK pathway mediates EGR-1-HSP70-dependent cigarette smoke-induced chemokine production. Am J Physiol Lung Cell Mol Physiol 292(5):L1297-1303.

Lin SC, Lu SY, Lee SY, Lin CY, Chen CH, Chang KW (2005). Areca (betel) nut extract activates mitogen-activated protein kinases and NF-kappaB in oral keratinocytes. Int J Cancer 116(4):526-535.

Lin SH, Chiou SJ, Ho WT, Chuang CT, Chuang LY, Guh JY (2016). Arecoline-induced pro-fibrotic proteins in LLC-PK1 cells are dependent on c-Jun N-terminal kinase. Toxicology 344-346(53-60.

Liu X, Gai Y, Liu F, Gao W, Zhang Y, Xu M et al. (2010). Trimetazidine inhibits pressure overload-induced cardiac fibrosis through NADPH oxidase-ROS-CTGF pathway. Cardiovasc Res 88(1):150-158.

Lohoff M, Giaisi M, Kohler R, Casper B, Krammer PH, Li-Weber M (2010). Early growth response protein-1 (Egr-1) is preferentially expressed in T helper type 2 (Th2) cells and is involved in acute transcription of the Th2 cytokine interleukin-4. J Biol Chem 285(3):1643-1652.

Ma RH, Tsai CC, Shieh TY (1995). Increased lysyl oxidase activity in fibroblasts cultured from oral submucous fibrosis associated with betel nut chewing in Taiwan. J Oral Pathol Med 24(9):407-412.

Maher R, Lee AJ, Warnakulasuriya KA, Lewis JA, Johnson NW (1994). Role of areca nut in the causation of oral submucous fibrosis: a case-control study in Pakistan. J Oral Pathol Med 23(2):65-69.

Massague J (1998). TGF-beta signal transduction. Annu Rev Biochem 67(753-791.

Mead AL, Wong TT, Cordeiro MF, Anderson IK, Khaw PT (2003). Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Invest Ophthalmol Vis Sci 44(8):3394-3401.

Meurer SK, Esser M, Tihaa L, Weiskirchen R (2012). BMP-7/TGF-beta1 signalling in myoblasts: components involved in signalling and BMP-7-dependent blockage of TGF-beta-mediated CTGF expression. Eur J Cell Biol 91(6-7):450-463.

Midgley VC, Khachigian LM (2004). Fibroblast growth factor-2 induction of platelet-derived growth factor-C chain transcription in vascular smooth muscle cells is ERK-dependent but not JNK-dependent and mediated by Egr-1. J Biol Chem 279(39):40289-40295.

Milbrandt J (1987). A nerve growth factor-induced gene encodes a possible transcriptional regulatory factor. Science 238(4828):797-799.

Mitroulis I, Kambas K, Anyfanti P, Doumas M, Ritis K (2011). The multivalent activity of the tissue factor-thrombin pathway in thrombotic and non-thrombotic disorders as a target for therapeutic intervention. Expert Opin Ther Targets 15(1):75-89.

Moon JA, Kim HT, Cho IS, Sheen YY, Kim DK (2006). IN-1130, a novel transforming growth factor-beta type I receptor kinase (ALK5) inhibitor, suppresses renal fibrosis in obstructive nephropathy. Kidney Int 70(7):1234-1243.

Moon Y, Lee M, Yang H (2007). Involvement of early growth response gene 1 in the modulation of microsomal prostaglandin E synthase 1 by epigallocatechin gallate in A549 human pulmonary epithelial cells. Biochem Pharmacol 73(1):125-135.

Morawetz G, Katsikeris N, Weinberg S, Listrom R (1987). Oral submucous fibrosis. Int J Oral Maxillofac Surg 16(5):609-614.

Moutasim KA, Jenei V, Sapienza K, Marsh D, Weinreb PH, Violette SM et al. (2011). Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis. J Pathol 223(3):366-377.

Murakami C, Hirakawa Y, Inui H, Nakano Y, Yoshida H (2002). Effect of tea catechins on cellular lipid peroxidation and cytotoxicity in HepG2 cells. Biosci Biotechnol Biochem 66(7):1559-1562.

Murphy-Ullrich JE, Poczatek M (2000). Activation of latent TGF-beta by thrombospondin-1: mechanisms and physiology. Cytokine Growth Factor Rev 11(1-2):59-69.

Murti PR, Bhonsle RB, Pindborg JJ, Daftary DK, Gupta PC, Mehta FS (1985). Malignant transformation rate in oral submucous fibrosis over a 17-year period. Community Dent Oral Epidemiol 13(6):340-341.

Murti PR, Bhonsle RB, Gupta PC, Daftary DK, Pindborg JJ, Mehta FS (1995). Etiology of oral submucous fibrosis with special reference to the role of areca nut chewing. J Oral Pathol Med 24(4):145-152.

Nagle DG, Ferreira D, Zhou YD (2006). Epigallocatechin-3-gallate (EGCG): chemical and biomedical perspectives. Phytochemistry 67(17):1849-1855.

Nakamura T, Sakata R, Ueno T, Sata M, Ueno H (2000). Inhibition of transforming growth factor beta prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatology 32(2):247-255.

Ni WF, Tsai CH, Yang SF, Chang YC (2007). Elevated expression of NF-kappaB in oral submucous fibrosis--evidence for NF-kappaB induction by safrole in human buccal mucosal fibroblasts. Oral Oncol 43(6):557-562.

Paradis V, Dargere D, Vidaud M, De Gouville AC, Huet S, Martinez V et al. (1999). Expression of connective tissue growth factor in experimental rat and human liver fibrosis. Hepatology 30(4):968-976.

Park JS, Khoi PN, Joo YE, Lee YH, Lang SA, Stoeltzing O et al. (2013). EGCG inhibits recepteur d''origine nantais expression by suppressing Egr-1 in gastric cancer cells. Int J Oncol 42(3):1120-1126.

Petersen M, Thorikay M, Deckers M, van Dinther M, Grygielko ET, Gellibert F et al. (2008). Oral administration of GW788388, an inhibitor of TGF-beta type I and II receptor kinases, decreases renal fibrosis. Kidney Int 73(6):705-715.

Phanish MK, Wahab NA, Hendry BM, Dockrell ME (2005). TGF-beta1-induced connective tissue growth factor (CCN2) expression in human renal proximal tubule epithelial cells requires Ras/MEK/ERK and Smad signalling. Nephron Exp Nephrol 100(4):e156-165.

Pindborg JJ, Sirsat SM (1966). Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol 22(6):764-779.

Prime SS, Pring M, Davies M, Paterson IC (2004). TGF-beta signal transduction in oro-facial health and non-malignant disease (part I). Crit Rev Oral Biol Med 15(6):324-336.

Pritchard MT, Nagy LE (2010). Hepatic fibrosis is enhanced and accompanied by robust oval cell activation after chronic carbon tetrachloride administration to Egr-1-deficient mice. Am J Pathol 176(6):2743-2752.

Qin S, Klamar CR, Fallert Junecko BA, Craigo J, Fuller DH, Reinhart TA (2013). Functional characterization of ferret CCL20 and CCR6 and identification of chemotactic inhibitors. Cytokine 61(3):924-932.

Rajalalitha P, Vali S (2005). Molecular pathogenesis of oral submucous fibrosis--a collagen metabolic disorder. J Oral Pathol Med 34(6):321-328.

Rajendran R (1994). Oral submucous fibrosis: etiology, pathogenesis, and future research. Bull World Health Organ 72(6):985-996.

Reichart PA, Phillipsen HP (1998). Betel chewer''s mucosa--a review. J Oral Pathol Med 27(6):239-242.

Remst DF, Blaney Davidson EN, Vitters EL, Bank RA, van den Berg WB, van der Kraan PM (2014). TGF-ss induces Lysyl hydroxylase 2b in human synovial osteoarthritic fibroblasts through ALK5 signaling. Cell Tissue Res 355(1):163-171.

Rhyu DY, Yang Y, Ha H, Lee GT, Song JS, Uh ST et al. (2005). Role of reactive oxygen species in TGF-beta1-induced mitogen-activated protein kinase activation and epithelial-mesenchymal transition in renal tubular epithelial cells. J Am Soc Nephrol 16(3):667-675.

Ricupero DA, Rishikof DC, Kuang PP, Poliks CF, Goldstein RH (1999). Regulation of connective tissue growth factor expression by prostaglandin E(2). Am J Physiol 277(6 Pt 1):L1165-1171.

Rifkin DB (2005). Latent transforming growth factor-beta (TGF-beta) binding proteins: orchestrators of TGF-beta availability. J Biol Chem 280(9):7409-7412.

Rossler OG, Thiel G (2009). Thrombin induces Egr-1 expression in fibroblasts involving elevation of the intracellular Ca2+ concentration, phosphorylation of ERK and activation of ternary complex factor. BMC Mol Biol 10(40.

Samarakoon R, Dobberfuhl AD, Cooley C, Overstreet JM, Patel S, Goldschmeding R et al. (2013). Induction of renal fibrotic genes by TGF-beta1 requires EGFR activation, p53 and reactive oxygen species. Cell Signal 25(11):2198-2209.

Schmierer B, Hill CS (2007). TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility. Nat Rev Mol Cell Biol 8(12):970-982.

Schultze-Mosgau S, Kopp J, Thorwarth M, Rodel F, Melnychenko I, Grabenbauer GG et al. (2006). Plasminogen activator inhibitor-I-related regulation of procollagen I (alpha1 and alpha2) by antitransforming growth factor-beta1 treatment during radiation-impaired wound healing. Int J Radiat Oncol Biol Phys 64(1):280-288.

Scutt A, Meghji S, Canniff JP, Harvey W (1987). Stabilisation of collagen by betel nut polyphenols as a mechanism in oral submucous fibrosis. Experientia 43(4):391-393.

Seedat HA, van Wyk CW (1988). Betel-nut chewing and submucous fibrosis in Durban. S Afr Med J 74(11):568-571.

Serrander L, Cartier L, Bedard K, Banfi B, Lardy B, Plastre O et al. (2007). NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation. Biochem J 406(1):105-114.

Shah N, Sharma PP (1998). Role of chewing and smoking habits in the etiology of oral submucous fibrosis (OSF): a case-control study. J Oral Pathol Med 27(10):475-479.

Shen K, Feng X, Su R, Xie H, Zhou L, Zheng S (2015). Epigallocatechin 3-gallate ameliorates bile duct ligation induced liver injury in mice by modulation of mitochondrial oxidative stress and inflammation. PLoS One 10(5):e0126278.

Sheng R, Gu ZL, Xie ML, Zhou WX, Guo CY (2010). Epigallocatechin gallate protects H9c2 cardiomyoblasts against hydrogen dioxides- induced apoptosis and telomere attrition. Eur J Pharmacol 641(2-3):199-206.

Shi Y, Massague J (2003). Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113(6):685-700.

Shiau YY, Kwan HW (1979). Submucous fibrosis in Taiwan. Oral Surg Oral Med Oral Pathol 47(5):453-457.

Shieh DH, Chiang LC, Lee CH, Yang YH, Shieh TY (2004). Effects of arecoline, safrole, and nicotine on collagen phagocytosis by human buccal mucosal fibroblasts as a possible mechanism for oral submucous fibrosis in Taiwan. J Oral Pathol Med 33(9):581-587.

Siegel-Axel DI (2003). Cerivastatin: a cellular and molecular drug for the future? Cell Mol Life Sci 60(1):144-164.

Sirsat SM, Pindborg JJ (1967). Subepithelial changes in oral submucous fibrosis. Acta Pathol Microbiol Scand 70(2):161-173.

Smith A, Giunta B, Bickford PC, Fountain M, Tan J, Shytle RD (2010). Nanolipidic particles improve the bioavailability and alpha-secretase inducing ability of epigallocatechin-3-gallate (EGCG) for the treatment of Alzheimer''s disease. Int J Pharm 389(1-2):207-212.

Sriram N, Kalayarasan S, Sudhandiran G (2009). Epigallocatechin-3-gallate exhibits anti-fibrotic effect by attenuating bleomycin-induced glycoconjugates, lysosomal hydrolases and ultrastructural changes in rat model pulmonary fibrosis. Chem Biol Interact 180(2):271-280.

Subramani T, Rathnavelu V, Alitheen NB (2013). The possible potential therapeutic targets for drug induced gingival overgrowth. Mediators Inflamm 2013(639468.

Sullivan BP, Cui W, Copple BL, Luyendyk JP (2012). Early growth response factor-1 limits biliary fibrosis in a model of xenobiotic-induced cholestasis in mice. Toxicol Sci 126(1):267-274.

Sume SS, Kantarci A, Lee A, Hasturk H, Trackman PC (2010). Epithelial to mesenchymal transition in gingival overgrowth. Am J Pathol 177(1):208-218.

Sun S, Ning X, Zhai Y, Du R, Lu Y, He L et al. (2014). Egr-1 mediates chronic hypoxia-induced renal interstitial fibrosis via the PKC/ERK pathway. Am J Nephrol 39(5):436-448.

Sundqvist K, Liu Y, Nair J, Bartsch H, Arvidson K, Grafstrom RC (1989). Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells. Cancer Res 49(19):5294-5298.

Surh YJ, Kundu JK, Na HK, Lee JS (2005). Redox-sensitive transcription factors as prime targets for chemoprevention with anti-inflammatory and antioxidative phytochemicals. J Nutr 135(12 Suppl):2993S-3001S.

Tak J, Gupta N, Bali R (2014). Oral submucous fibrosis: a review article on etiopathogenesis. Kathmandu Univ Med J (KUMJ) 12(46):153-156.

Teekakirikul P, Eminaga S, Toka O, Alcalai R, Wang L, Wakimoto H et al. (2010). Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-beta. J Clin Invest 120(10):3520-3529.

Thangjam GS, Agarwal P, Khan I, Verma UP, Balapure AK, Rao SG et al. (2009). Transglutaminase-2 regulation by arecoline in gingival fibroblasts. J Dent Res 88(2):170-175.

Thompson K, Hamilton DW, Leask A (2010). ALK5 inhibition blocks TGFss-induced CCN2 expression in gingival fibroblasts. J Dent Res 89(12):1450-1454.

Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S (2006). Oral submucous fibrosis: review on aetiology and pathogenesis. Oral Oncol 42(6):561-568.

Tipoe GL, Leung TM, Liong EC, Lau TY, Fung ML, Nanji AA (2010). Epigallocatechin-3-gallate (EGCG) reduces liver inflammation, oxidative stress and fibrosis in carbon tetrachloride (CCl4)-induced liver injury in mice. Toxicology 273(1-3):45-52.

Tobar N, Toyos M, Urra C, Mendez N, Arancibia R, Smith PC et al. (2014). c-Jun N terminal kinase modulates NOX-4 derived ROS production and myofibroblasts differentiation in human breast stromal cells. BMC Cancer 14(640.

Trivedy C, Baldwin D, Warnakulasuriya S, Johnson N, Peters T (1997). Copper content in Areca catechu (betel nut) products and oral submucous fibrosis. Lancet 349(9063):1447.

Trivedy CR, Warnakulasuriya KA, Peters TJ, Senkus R, Hazarey VK, Johnson NW (2000). Raised tissue copper levels in oral submucous fibrosis. J Oral Pathol Med 29(6):241-248.

Tsai CC, Ma RH, Shieh TY (1999). Deficiency in collagen and fibronectin phagocytosis by human buccal mucosa fibroblasts in vitro as a possible mechanism for oral submucous fibrosis. J Oral Pathol Med 28(2):59-63.

Tsai CH, Chou MY, Chang YC (2003). The up-regulation of cyclooxygenase-2 expression in human buccal mucosal fibroblasts by arecoline: a possible role in the pathogenesis of oral submucous fibrosis. J Oral Pathol Med 32(3):146-153.

Tsai CH, Yang SF, Chen YJ, Chu SC, Hsieh YS, Chang YC (2004). Regulation of interleukin-6 expression by arecoline in human buccal mucosal fibroblasts is related to intracellular glutathione levels. Oral Dis 10(6):360-364.

Tsai CH, Yang SF, Chen YJ, Chou MY, Chang YC (2005a). The upregulation of insulin-like growth factor-1 in oral submucous fibrosis. Oral Oncol 41(9):940-946.

Tsai CH, Yang SF, Chen YJ, Chou MY, Chang YC (2005b). Raised keratinocyte growth factor-1 expression in oral submucous fibrosis in vivo and upregulated by arecoline in human buccal mucosal fibroblasts in vitro. J Oral Pathol Med 34(2):100-105.

Tsai CH, Yang SF, Lee SS, Chang YC (2009). Augmented heme oxygenase-1 expression in areca quid chewing-associated oral submucous fibrosis. Oral Dis 15(4):281-286.

Umbarkar P, Singh S, Arkat S, Bodhankar SL, Lohidasan S, Sitasawad SL (2015). Monoamine oxidase-A is an important source of oxidative stress and promotes cardiac dysfunction, apoptosis, and fibrosis in diabetic cardiomyopathy. Free Radic Biol Med 87(263-273.

Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007). Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39(1):44-84.

Van Geest RJ, Klaassen I, Vogels IM, Van Noorden CJ, Schlingemann RO (2010). Differential TGF-{beta} signaling in retinal vascular cells: a role in diabetic retinopathy? Invest Ophthalmol Vis Sci 51(4):1857-1865.

von Lohneysen K, Noack D, Hayes P, Friedman JS, Knaus UG (2012). Constitutive NADPH oxidase 4 activity resides in the composition of the B-loop and the penultimate C terminus. J Biol Chem 287(12):8737-8745.

Wang CY, Deng YT, Huang SY, Liu CM, Chang HH, Wong MY (2014). Epigallocatechin-3-gallate inhibits lysophosphatidic acid-stimulated connective tissue growth factor via JNK and Smad3 suppression in human gingival fibroblasts. J Formos Med Assoc 113(1):50-55.

Wei J, Bhattacharyya S, Tourtellotte WG, Varga J (2011). Fibrosis in systemic sclerosis: emerging concepts and implications for targeted therapy. Autoimmun Rev 10(5):267-275.

Weng HL, Ciuclan L, Liu Y, Hamzavi J, Godoy P, Gaitantzi H et al. (2007). Profibrogenic transforming growth factor-beta/activin receptor-like kinase 5 signaling via connective tissue growth factor expression in hepatocytes. Hepatology 46(4):1257-1270.

Wu KJ, Huang GF, Chen CH, Chang HH, Deng YT (2014). Cyclosporine A induces connective tissue growth factor expression in human gingival fibroblasts: suppression by epigallocatechin-3-gallate. J Formos Med Assoc 113(11):828-832.

Wu M, Melichian DS, Chang E, Warner-Blankenship M, Ghosh AK, Varga J (2009a). Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator-activated receptor-gamma. Am J Pathol 174(2):519-533.

Wu M, Melichian DS, de la Garza M, Gruner K, Bhattacharyya S, Barr L et al. (2009b). Essential roles for early growth response transcription factor Egr-1 in tissue fibrosis and wound healing. Am J Pathol 175(3):1041-1055.

Wynn TA, Ramalingam TR (2012). Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med 18(7):1028-1040.

Xie S, Sukkar MB, Issa R, Oltmanns U, Nicholson AG, Chung KF (2005). Regulation of TGF-beta 1-induced connective tissue growth factor expression in airway smooth muscle cells. Am J Physiol Lung Cell Mol Physiol 288(1):L68-76.

Yamada M, Kuwano K, Maeyama T, Yoshimi M, Hamada N, Fukumoto J et al. (2007). Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis. J Clin Pathol 60(8):916-920.

Yamaguchi Y, Takihara T, Chambers RA, Veraldi KL, Larregina AT, Feghali-Bostwick CA (2012). A peptide derived from endostatin ameliorates organ fibrosis. Sci Transl Med 4(136):136ra171.

Yamamoto T, Takagawa S, Katayama I, Nishioka K (1999). Anti-sclerotic effect of transforming growth factor-beta antibody in a mouse model of bleomycin-induced scleroderma. Clin Immunol 92(1):6-13.

Yan SF, Lu J, Xu L, Zou YS, Tongers J, Kisiel W et al. (2000). Pulmonary expression of early growth response-1: biphasic time course and effect of oxygen concentration. J Appl Physiol (1985) 88(6):2303-2309.

Yang SF, Hsieh YS, Tsai CH, Chou MY, Chang YC (2003). The upregulation of type I plasminogen activator inhibitor in oral submucous fibrosis. Oral Oncol 39(4):367-372.

Yang SF, Tsai CH, Chang YC (2008). The upregulation of heat shock protein 47 expression in human buccal fibroblasts stimulated with arecoline. J Oral Pathol Med 37(4):206-210.

Yang WH, Kuo MY, Liu CM, Deng YT, Chang HH, Chang JZ (2013). Curcumin inhibits TGFbeta1-induced CCN2 via Src, JNK, and Smad3 in gingiva. J Dent Res 92(7):629-634.

Yang WH, Deng YT, Hsieh YP, Wu KJ, Kuo MY (2015). NADPH Oxidase 4 Mediates TGFbeta1-induced CCN2 in Gingival Fibroblasts. J Dent Res 94(7):976-982.

Yasuoka H, Hsu E, Ruiz XD, Steinman RA, Choi AM, Feghali-Bostwick CA (2009). The fibrotic phenotype induced by IGFBP-5 is regulated by MAPK activation and egr-1-dependent and -independent mechanisms. Am J Pathol 175(2):605-615.

Yu CC, Tsai CH, Hsu HI, Chang YC (2013). Elevation of S100A4 expression in buccal mucosal fibroblasts by arecoline: involvement in the pathogenesis of oral submucous fibrosis. PLoS One 8(1):e55122.

Yu J, Mao S, Zhang Y, Gong W, Jia Z, Huang S et al. (2016). MnTBAP Therapy Attenuates Renal Fibrosis in Mice with 5/6 Nephrectomy. Oxid Med Cell Longev 2016(7496930.





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