跳到主要內容

臺灣博碩士論文加值系統

(44.200.86.95) 您好!臺灣時間:2024/05/28 09:26
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:黃鈞源
研究生(外文):Jyun-Yuan Huang
論文名稱:細胞內微小核糖核酸-130a藉由減少PGC1-alpha及PPAR-gamma以抑制 B型肝炎病毒之複製
論文名稱(外文):MicroRNA-130a Can Inhibit Hepatitis B Virus Replication Via Targeting PGC1-alpha And PPAR-gamma
指導教授:施嘉和
指導教授(外文):Chiaho Shih
口試委員:林文昌楊文欽陳儀莊鄒安平黃麗華莊立民
口試委員(外文):Wen-chang LinWen-Chin YangYijuang ChernAnn-Ping TsouLih-Hwa HwangLi-Ming Chuang
口試日期:2015-05-15
學位類別:博士
校院名稱:國防醫學院
系所名稱:生命科學研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2015
畢業學年度:103
語文別:英文
論文頁數:104
中文關鍵詞:B型肝炎病毒微小核糖核酸
外文關鍵詞:Hepatitis B VirusmicroRNA-130aPPARGC1aPPARgmetabolisminflammation
相關次數:
  • 被引用被引用:0
  • 點閱點閱:209
  • 評分評分:
  • 下載下載:3
  • 收藏至我的研究室書目清單書目收藏:0
近來,細胞內微小核醣核酸(microRNA)與致病性病毒之間的相互關係成為病毒學的熱門研究領域之一,而微小核糖核酸調節他們的目標訊息核糖核酸(mRNA)是利用序列專一的特性。一般來說,微小核糖核酸可直接附著於目標訊息核糖核酸的3端非轉譯區域( 3’UTR),而此結合會造成目標訊息核糖核酸的裂解或是其轉譯反應被抑制。目前越來越多證據顯示,細胞微小核糖核酸也可干擾細胞內RNA或是DNA病毒進行複製。儘管有文獻指出某些微小核醣核酸能影響B型肝炎病毒的複製,不過目前對於細胞微小核糖核酸影響B型肝炎病毒的相關研究仍未完全明瞭,也需要更多的驗證。在本論文中,我們藉由比較B型肝炎病毒感染之肝臟細胞株與正常肝臟細胞株中,微小核糖核酸的表現差異情形。之後發現在B型肝炎病毒感染的肝臟細胞株中,細胞內微小核糖核酸-130a (miR-130a)的表現量明顯降低。然而,若在肝臟細胞中高度表現微小核糖核酸-130a 則會顯著地抑制B型肝炎病毒的複製能力,經研究發現是因微小核糖核酸-130a 透過抑制兩個可調控B型肝炎病毒複製的重要代謝因子PGC1a 和 PPARg 所造成。反之,B型肝炎病毒也可利用減少微小核糖核酸-130a 的表現來增加細胞內PGC1a 和PPARg 的蛋白表現量,進而促進病毒本身的複製。因此,三者之間形成獨特的正向迴饋迴路。接著我們也發現NF-kB/p65可藉著活化微小核糖核酸-130a上游的啟動子而促進其表現,然而微小核糖核酸-130a也可利用抑制PPARg 的表現量來避免NF-kB/p65 蛋白被分解。因此微小核糖核酸-130a、PPARg 和NF-kB/p65 彼此也形成第二個正向迴饋迴路。由研究結果推論當肝臟細胞產生發炎反應時,活化的NF-kB/p65 會增進微小核糖核酸-130a 的表現,進而去抑制病毒的複製。但在無徵狀B型肝炎帶原者中,因持續性的病毒感染會降低微小核糖核酸-130a 的表現及抑制NF-kB 訊息傳遞路徑,因而減輕發炎反應及造成免疫耐受性的發生。除此之外,我們也發現微小核糖核酸-130a 也藉著同時抑制PGC1a和 PPARg 而影響肝臟代謝狀態的平衡。
Recently, the interactions between cellular microRNAs (miRNAs) and infectious diseases have become a hot field in virology. These miRNAs can regulate their target mRNAs in a sequence specific manner. In general, direct targeting at the 3’UTR of mRNA by miRNA can result in mRNA degradation or translational suppression. Accumulating researches indicate that miRNAs can often participate in the replication of both RNA and DNA viruses. In this thesis, we found one cellular microRNA, miR-130a, expression was significantly reduced in hepatitis B virus (HBV)-replicating hepatocytes and transgenic mice. Conversely, overexpression of miR-130a significantly inhibited HBV DNA replication and protein synthesis. Using bioinformatic analysis and 3’UTR reporter assay, we found that miR-130a reduced HBV replication by targeting at two major transcription factors, PGC1a and PPARg, both of which can potently stimulate HBV replication. The relationship between HBV, miR-130a, PPARg and PGC1a like a special positive feed-forward loop. HBV can significantly enhance viral replication by reducing miR-130a expression and increasing PGC1a and PPARg. Furthermore, we also identified that NF-kB/p65 can strongly stimulate miR-130a expression through the binding site on miR-130a promoter. Interestingly, miR-130a can promote NF-kB/p65 protein level by reducing PPARg which can induce NF-kB/p65 protein degradation. We proposed that the second positive feed-forward loop between miR-130a and NF-kB/p65 via PPARg. In our model, activation of NF-kB signaling, like liver inflammation, could contribute to viral clearance via its positive effect on miR-130a transcription. However, persistent viral infection in asymptomatic HBV carriers have lower miR-130a and NF-kB expression, leading to dampened inflammation and immune response. Because of PGC1a and PPARg both were critical regulators in glucose and lipid metabolism, miR-130a could also contribute to metabolic homeostasis by dual targeting PGC1a and PPARg simultaneously.
中文摘要……………………………………………………………….……....Ⅶ
Abstract………………………………………………………………….….…Ⅸ
1. Introduction…………………………………………………………...……..1
1.1 Biogenesis and functions of microRNAs……………………………………1
1.2 Liver-related microRNAs……………………………………………………3
1.3 Transcription and replication of HBV……………………………………….4
1.4 Interaction between microRNA and virus…………………………………...7
1.5 Biological roles of micorRNA-130a………………………………………...8
1.6 Peroxisome Proliferator activated receptors gamma……………………….12
1.7 The functions and regulations of PPARGC1PGC1)…………………..14
2. Material and Methods………………………………………………..…….18
2.1 Ethics Statement………………………………………………………...….18
2.2 Animals experiments……………………………………………………… 18
2.3 Construction of miRNA-expressing plasmids……………………………. .18
2.4 Source of antibodies………………………………………………………..19
2.5 Construction of miR-130a sponge…………………………………………20
2.6 Cell Culture……………………………………………………..…………20
2.7 PPARγ agonist and antagonist……………………………………………..21
2.8 Quantitative Real-time PCR……………………………………………….21
2.9 Stem-loop qPCR for miRNA………………………………………………22
2.10 Southern and Northern blot……………………………………………….22
2.11 MiR-130a promoter analysis by deletion mapping……………………….22
2.12 Stable miR-130a expressing cell lines……………………………………23
2.13 LNA-miR-130a knockdown………………………………………………24
2.14 Bioinformatic analysis……………………………………………………24
2.15 MicroRNA Taqman low density array analysis…………………………..25
2.16 Bioinformatic analysis of NF-B/p65 promoter………………………….25
2.17 Statistics…………………………………………………………………..25
3. Results…………………………………………………………………..…..27
3.1 Identification of anti-HBV cellular microRNAs…………………………...27
3.2 Viral replication and gene expression attenuated by miR-130a……………28
3.3 Reduction of endogenous miR-130a enhanced HBV DNA replication and protein expression………………………………………………………….29
3.4 MiR-130a can knockdown HBV RNA indirectly………………………….30
3.5 MiR-130a directly targets at both PGC1and PPAR…………………….31
3.6 Stimulatory effect of PPAR and PGC1on enhancing HBV DNA replication………………………………………………………………….34
3.7 MiR-130a in hepatic gluconeogenesis and lipogenesis……………………38
3.8 HBV transgenic mice exhibited reduced levels of miR-130a……………..40
4. Discussion…………………………………………………………………..41
5. References………………………………………………………………….48
References
Aden DP, Fogel A, Plotkin S, Damjanov I, Knowles BB (1979) Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature 282: 615-616

Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, Evans RM (2013) PPARgamma signaling and metabolism: the good, the bad and the future. Nature medicine 19: 557-566

Ambros V (2011) MicroRNAs and developmental timing. Current opinion in genetics & development 21: 511-517
Andersson U, Scarpulla RC (2001) Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Molecular and cellular biology 21: 3738-3749

Bai S, Nasser MW, Wang B, Hsu SH, Datta J, Kutay H, Yadav A, Nuovo G, Kumar P, Ghoshal K (2009) MicroRNA-122 inhibits tumorigenic properties of hepatocellular carcinoma cells and sensitizes these cells to sorafenib. The Journal of biological chemistry 284: 32015-32027

Bar-Yishay I, Shaul Y, Shlomai A (2011) Hepatocyte metabolic signalling pathways and regulation of hepatitis B virus expression. Liver international 31: 282-290

Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136: 215-233

Bertoletti A, Ferrari C, Fiaccadori F, Penna A, Margolskee R, Schlicht HJ, Fowler P, Guilhot S, Chisari FV (1991) HLA class I-restricted human cytotoxic T cells recognize endogenously synthesized hepatitis B virus nucleocapsid antigen. Proceedings of the National Academy of Sciences of the United States of America 88: 10445-10449

Bhanja Chowdhury J, Shrivastava S, Steele R, Di Bisceglie AM, Ray R, Ray RB (2012) Hepatitis C virus infection modulates expression of interferon stimulatory gene IFITM1 by upregulating miR-130A. Journal of virology 86: 10221-10225

Biermer M, Puro R, Schneider RJ (2003) Tumor necrosis factor alpha inhibition of hepatitis B virus replication involves disruption of capsid Integrity through activation of NF-kappaB. Journal of virology 77: 4033-4042

Boll K, Reiche K, Kasack K, Morbt N, Kretzschmar AK, Tomm JM, Verhaegh G, Schalken J, von Bergen M, Horn F, Hackermuller J (2013) MiR-130a, miR-203 and miR-205 jointly repress key oncogenic pathways and are downregulated in prostate carcinoma. Oncogene 32: 277-285

Budkowska A (1977) Immunochemical and morphological studies of hepatitis B core antigen isolated from the nuclei of hepatocytes. The Journal of infectious diseases 135: 463-467

Chen CC, Ko TM, Ma HI, Wu HL, Xiao X, Li J, Chang CM, Wu PY, Chen CH, Han JM, Yu CP, Jeng KS, Hu CP, Tao MH (2007) Long-term inhibition of hepatitis B virus in transgenic mice by double-stranded adeno-associated virus 8-delivered short hairpin RNA. Gene therapy 14: 11-19

Chen CL, Yang HI, Yang WS, Liu CJ, Chen PJ, You SL, Wang LY, Sun CA, Lu SN, Chen DS, Chen CJ (2008) Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology 135: 111-121

Chen HL, Huang JY, Chen CM, Chu TH, Shih C (2012) MicroRNA-22 can reduce parathymosin expression in transdifferentiated hepatocytes. PloS one 7: e34116

Chiang CH, Yang HI, Jen CL, Lu SN, Wang LY, You SL, Su J, Iloeje UH, Chen CJ, Group R-HS (2013) Association between obesity, hypertriglyceridemia and low hepatitis B viral load. International journal of obesity 37: 410-415

Chisari FV, Ferrari C (1995) Hepatitis B virus immunopathogenesis. Annual review of immunology 13: 29-60

Cho N, Momose Y (2008) Peroxisome proliferator-activated receptor gamma agonists as insulin sensitizers: from the discovery to recent progress. Current topics in medicinal chemistry 8: 1483-1507

Chua PK, Tang FM, Huang JY, Suen CS, Shih C (2010) Testing the balanced electrostatic interaction hypothesis of hepatitis B virus DNA synthesis by using an in vivo charge rebalance approach. Journal of virology 84: 2340-2351

Eisele PS, Salatino S, Sobek J, Hottiger MO, Handschin C (2013) The peroxisome proliferator-activated receptor gamma coactivator 1alpha/beta (PGC-1) coactivators repress the transcriptional activity of NF-kappaB in skeletal muscle cells. The Journal of biological chemistry 288: 2246-2260

Ely A, Naidoo T, Arbuthnot P (2009) Efficient silencing of gene expression with modular trimeric Pol II expression cassettes comprising microRNA shuttles. Nucleic acids research 37: e91

Esau C, Davis S, Murray SF, Yu XX, Pandey SK, Pear M, Watts L, Booten SL, Graham M, McKay R, Subramaniam A, Propp S, Lollo BA, Freier S, Bennett CF, Bhanot S, Monia BP (2006) miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. Cell metabolism 3: 87-98

Finck BN, Kelly DP (2006) PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. The Journal of clinical investigation 116: 615-622

Fuchs Y, Brunwasser M, Haif S, Haddad J, Shneyer B, Goldshmidt-Tran O, Korsensky L, Abed M, Zisman-Rozen S, Koren L, Carmi Y, Apte R, Yang RB, Orian A, Bejar J, Ron D (2012) Sef is an inhibitor of proinflammatory cytokine signaling, acting by cytoplasmic sequestration of NF-kappaB. Developmental cell 23: 611-623

Galibert F, Mandart E, Fitoussi F, Tiollais P, Charnay P (1979) Nucleotide sequence of the hepatitis B virus genome (subtype ayw) cloned in E. coli. Nature 281: 646-650

Ganem D, Prince AM (2004) Hepatitis B virus infection--natural history and clinical consequences. The New England journal of medicine 350: 1118-1129

Goldstein BJ (2000) Rosiglitazone. International journal of clinical practice 54: 333-337

Guidotti LG, Ando K, Hobbs MV, Ishikawa T, Runkel L, Schreiber RD, Chisari FV (1994) Cytotoxic T lymphocytes inhibit hepatitis B virus gene expression by a noncytolytic mechanism in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 91: 3764-3768

Hager M, Pedersen CC, Larsen MT, Andersen MK, Hother C, Gronbaek K, Jarmer H, Borregaard N, Cowland JB (2011) MicroRNA-130a-mediated down-regulation of Smad4 contributes to reduced sensitivity to TGF-beta1 stimulation in granulocytic precursors. Blood 118: 6649-6659

Hand NJ, Master ZR, Le Lay J, Friedman JR (2009) Hepatic function is preserved in the absence of mature microRNAs. Hepatology 49: 618-626

Hayden GS (2004) Signaling to NF-kappaB. Genes Dev 18: 2195-2224

Hou Y, Moreau F, Chadee K (2012) PPARgamma is an E3 ligase that induces the degradation of NFkappaB/p65. Nature communications 3: 1300

Hsu CS, Liu CH, Wang CC, Tseng TC, Liu CJ, Chen CL, Chen PJ, Chen DS, Kao JH (2012a) Impact of hepatitis B virus infection on metabolic profiles and modifying factors. Journal of viral hepatitis 19: e48-57

Hsu CS, Liu WL, Chao YC, Lin HH, Tseng TC, Wang CC, Chen DS, Kao JH (2015) Adipocytokines and liver fibrosis stages in patients with chronic hepatitis B virus infection. Hepatology international 9: 231-242

Hsu SH, Wang B, Kota J, Yu J, Costinean S, Kutay H, Yu L, Bai S, La Perle K, Chivukula RR, Mao H, Wei M, Clark KR, Mendell JR, Caligiuri MA, Jacob ST, Mendell JT, Ghoshal K (2012b) Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver. The Journal of clinical investigation 122: 2871-2883

Huang ZS, Huang TS, Wu TH, Chen MF, Hsu CS, Kao JH (2010) Asymptomatic chronic hepatitis B virus infection does not increase the risk of diabetes mellitus: a ten-year observation. Journal of gastroenterology and hepatology 25: 1420-1425
Iwasaki S, Kobayashi M, Yoda M, Sakaguchi Y, Katsuma S, Suzuki T, Tomari Y (2010) Hsc70/Hsp90 chaperone machinery mediates ATP-dependent RISC loading of small RNA duplexes. Molecular cell 39: 292-299

Jopling CL, Yi M, Lancaster AM, Lemon SM, Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA. Science 309: 1577-1581

Jung YJ, Kim JW, Park SJ, Min BY, Jang ES, Kim NY, Jeong SH, Shin CM, Lee SH, Park YS, Hwang JH, Kim N, Lee DH (2013) c-Myc-mediated overexpression of miR-17-92 suppresses replication of hepatitis B virus in human hepatoma cells. Journal of medical virology 85: 969-978

Kahn BB, McGraw TE (2010) Rosiglitazone, PPARgamma, and type 2 diabetes. The New England journal of medicine 363: 2667-2669

Karin M (2006) Nuclear factor-kappaB in cancer development and progression. Nature 441: 431-436

Kim GH, Samant SA, Earley JU, Svensson EC (2009) Translational control of FOG-2 expression in cardiomyocytes by microRNA-130a. PloS one 4: e6161

Koo SH, Satoh H, Herzig S, Lee CH, Hedrick S, Kulkarni R, Evans RM, Olefsky J, Montminy M (2004) PGC-1 promotes insulin resistance in liver through PPAR-alpha-dependent induction of TRB-3. Nature medicine 10: 530-534

Lau NC, Lim LP, Weinstein EG, Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294: 858-862

Le Pogam S, Chua PK, Newman M, Shih C (2005) Exposure of RNA templates and encapsidation of spliced viral RNA are influenced by the arginine-rich domain of human hepatitis B virus core antigen (HBcAg 165-173). Journal of virology 79: 1871-1887

Lee EK, Lee MJ, Abdelmohsen K, Kim W, Kim MM, Srikantan S, Martindale JL, Hutchison ER, Kim HH, Marasa BS, Selimyan R, Egan JM, Smith SR, Fried SK, Gorospe M (2011) miR-130 suppresses adipogenesis by inhibiting peroxisome proliferator-activated receptor gamma expression. Molecular and cellular biology 31: 626-638

Lee JR, Koretzky GA (1998) Production of reactive oxygen intermediates following CD40 ligation correlates with c-Jun N-terminal kinase activation and IL-6 secretion in murine B lymphocytes. European journal of immunology 28: 4188-4197

Leone TC, Lehman JJ, Finck BN, Schaeffer PJ, Wende AR, Boudina S, Courtois M, Wozniak DF, Sambandam N, Bernal-Mizrachi C, Chen Z, Holloszy JO, Medeiros DM, Schmidt RE, Saffitz JE, Abel ED, Semenkovich CF, Kelly DP (2005) PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS biology 3: e101

Li S, Duan X, Li Y, Liu B, McGilvray I, Chen L (2014) MicroRNA-130a inhibits HCV replication by restoring the innate immune response. Journal of viral hepatitis 21: 121-128

Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, Puigserver P, Isotani E, Olson EN, Lowell BB, Bassel-Duby R, Spiegelman BM (2002) Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature 418: 797-801

Liu Q, Yuan B, Lo KA, Patterson HC, Sun Y, Lodish HF (2012) Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism. Proceedings of the National Academy of Sciences of the United States of America 109: 14568-14573

Mason AL, Lau JY, Hoang N, Qian K, Alexander GJ, Xu L, Guo L, Jacob S, Regenstein FG, Zimmerman R, Everhart JE, Wasserfall C, Maclaren NK, Perrillo RP (1999) Association of diabetes mellitus and chronic hepatitis C virus infection. Hepatology 29: 328-333

Mayerson AB, Hundal RS, Dufour S, Lebon V, Befroy D, Cline GW, Enocksson S, Inzucchi SE, Shulman GI, Petersen KF (2002) The effects of rosiglitazone on insulin sensitivity, lipolysis, and hepatic and skeletal muscle triglyceride content in patients with type 2 diabetes. Diabetes 51: 797-802

Mehta SH, Brancati FL, Sulkowski MS, Strathdee SA, Szklo M, Thomas DL (2000) Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med 133: 592-599

Meng S, Cao J, Zhang X, Fan Y, Fang L, Wang C, Lv Z, Fu D, Li Y (2013) Downregulation of microRNA-130a contributes to endothelial progenitor cell dysfunction in diabetic patients via its target Runx3. PloS one 8: e68611

Michalik L, Wahli W (2008) PPARs Mediate Lipid Signaling in Inflammation and Cancer. PPAR research 2008: 134059
Miyoshi K, Miyoshi T, Hartig JV, Siomi H, Siomi MC (2010) Molecular mechanisms that funnel RNA precursors into endogenous small-interfering RNA and microRNA biogenesis pathways in Drosophila. Rna 16: 506-515

Mueller E, Drori S, Aiyer A, Yie J, Sarraf P, Chen H, Hauser S, Rosen ED, Ge K, Roeder RG, Spiegelman BM (2002) Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms. The Journal of biological chemistry 277: 41925-41930

Murakami K, Tobe K, Ide T, Mochizuki T, Ohashi M, Akanuma Y, Yazaki Y, Kadowaki T (1998) A novel insulin sensitizer acts as a coligand for peroxisome proliferator-activated receptor-alpha (PPAR-alpha) and PPAR-gamma: effect of PPAR-alpha activation on abnormal lipid metabolism in liver of Zucker fatty rats. Diabetes 47: 1841-1847

Nakabayashi H, Taketa K, Miyano K, Yamane T, Sato J (1982) Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer research 42: 3858-3863

Nassal M (1992) The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. Journal of virology 66: 4107-4116

Ondracek CR, Rushing CN, Reese VC, Oropeza CE, McLachlan A (2009) Peroxisome proliferator-activated receptor gamma Coactivator 1alpha and small heterodimer partner differentially regulate nuclear receptor-dependent hepatitis B virus biosynthesis. Journal of virology 83: 12535-12544

Osbourne A, Calway T, Broman M, McSharry S, Earley J, Kim GH (2014) Downregulation of connexin43 by microRNA-130a in cardiomyocytes results in cardiac arrhythmias. Journal of molecular and cellular cardiology 74: 53-63

Pascual G, Fong AL, Ogawa S, Gamliel A, Li AC, Perissi V, Rose DW, Willson TM, Rosenfeld MG, Glass CK (2005) A SUMOylation-dependent pathway mediates transrepression of inflammatory response genes by PPAR-gamma. Nature 437: 759-763

Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, Chisari FV, David M (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449: 919-922

Puigserver P, Rhee J, Donovan J, Walkey CJ, Yoon JC, Oriente F, Kitamura Y, Altomonte J, Dong H, Accili D, Spiegelman BM (2003) Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction. Nature 423: 550-555

Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92: 829-839

Qian J, Chen S, Huang Y, Shi X, Liu C (2013) PGC-1alpha regulates hepatic hepcidin expression and iron homeostasis in response to inflammation. Molecular endocrinology 27: 683-692

Qiu S, Lin S, Hu D, Feng Y, Tan Y, Peng Y (2013) Interactions of miR-323/miR-326/miR-329 and miR-130a/miR-155/miR-210 as prognostic indicators for clinical outcome of glioblastoma patients. Journal of translational medicine 11: 10

Quasdorff M, Protzer U (2010) Control of hepatitis B virus at the level of transcription. Journal of viral hepatitis 17: 527-536

Ruan H, Pownall HJ, Lodish HF (2003) Troglitazone antagonizes tumor necrosis factor-alpha-induced reprogramming of adipocyte gene expression by inhibiting the transcriptional regulatory functions of NF-kappaB. The Journal of biological chemistry 278: 28181-28192

Saito K, Kondo E, Matsushita M (2011) MicroRNA 130 family regulates the hypoxia response signal through the P-body protein DDX6. Nucleic acids research 39: 6086-6099

Seeger C, Mason WS (2015) Molecular biology of hepatitis B virus infection. Virology
Sekine S, Ogawa R, Ito R, Hiraoka N, McManus MT, Kanai Y, Hebrok M (2009) Disruption of Dicer1 induces dysregulated fetal gene expression and promotes hepatocarcinogenesis. Gastroenterology 136: 2304-2315.e2301-2304

Shih C (2013) Chronic hepatitis B and C : basic science to clinical applications, New Jersey: World Scientific.
Shih C, Yu MY, Li LS, Shih JW (1990) Hepatitis B virus propagated in a rat hepatoma cell line is infectious in a primate model. Virology 179: 871-873

Shih CH, Li LS, Roychoudhury S, Ho MH (1989) In vitro propagation of human hepatitis B virus in a rat hepatoma cell line. Proceedings of the National Academy of Sciences of the United States of America 86: 6323-6327

Shlomai A, Paran N, Shaul Y (2006) PGC-1alpha controls hepatitis B virus through nutritional signals. Proceedings of the National Academy of Sciences of the United States of America 103: 16003-16008

Shlomai A, Rechtman MM, Burdelova EO, Zilberberg A, Hoffman S, Solar I, Fishman S, Halpern Z, Sklan EH (2012) The metabolic regulator PGC-1alpha links hepatitis C virus infection to hepatic insulin resistance. Journal of hepatology 57: 867-873

Slagle BL, Andrisani OM, Bouchard MJ, Lee CG, Ou JH, Siddiqui A. (2014) Technical standards for hepatitis B virus X protein (HBx) research. Hepatology.

St-Pierre J, Drori S, Uldry M, Silvaggi JM, Rhee J, Jager S, Handschin C, Zheng K, Lin J, Yang W, Simon DK, Bachoo R, Spiegelman BM (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127: 397-408

St-Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB, Spiegelman BM (2003) Bioenergetic analysis of peroxisome proliferator-activated receptor gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. The Journal of biological chemistry 278: 26597-26603

Su F, Schneider RJ (1996) Hepatitis B virus HBx protein activates transcription factor NF-kappaB by acting on multiple cytoplasmic inhibitors of rel-related proteins. Journal of virology 70: 4558-4566

Tai DJ, Su CC, Ma YL, Lee EH (2009) SGK1 phosphorylation of IkappaB Kinase alpha and p300 Up-regulates NF-kappaB activity and increases N-Methyl-D-aspartate receptor NR2A and NR2B expression. The Journal of biological chemistry 284: 4073-4089

Tang L, Pu Y, Wong DK, Liu T, Tang H, Xiang T, Yuen MF, Ren G (2011) The hepatitis B virus-associated estrogen receptor alpha (ERalpha) was regulated by microRNA-130a in HepG2.2.15 human hepatocellular carcinoma cells. Acta biochimica et biophysica Sinica 43: 640-646

Tiollais P, Pourcel C, Dejean A (1985) The hepatitis B virus. Nature 317: 489-495

Tontonoz P, Hu E, Spiegelman BM (1995) Regulation of adipocyte gene expression and differentiation by peroxisome proliferator activated receptor gamma. Current opinion in genetics & development 5: 571-576

Tran M, Tam D, Bardia A, Bhasin M, Rowe GC, Kher A, Zsengeller ZK, Akhavan-Sharif MR, Khankin EV, Saintgeniez M, David S, Burstein D, Karumanchi SA, Stillman IE, Arany Z, Parikh SM (2011) PGC-1alpha promotes recovery after acute kidney injury during systemic inflammation in mice. The Journal of clinical investigation 121: 4003-4014

Tsai WC, Hsu SD, Hsu CS, Lai TC, Chen SJ, Shen R, Huang Y, Chen HC, Lee CH, Tsai TF, Hsu MT, Wu JC, Huang HD, Shiao MS, Hsiao M, Tsou AP (2012) MicroRNA-122 plays a critical role in liver homeostasis and hepatocarcinogenesis. The Journal of clinical investigation 122: 2884-2897

Wakui Y, Inoue J, Ueno Y, Fukushima K, Kondo Y, Kakazu E, Obara N, Kimura O, Shimosegawa T (2010) Inhibitory effect on hepatitis B virus in vitro by a peroxisome proliferator-activated receptor-gamma ligand, rosiglitazone. Biochemical and biophysical research communications 396: 508-514

Waris G, Huh KW, Siddiqui A (2001) Mitochondrially associated hepatitis B virus X protein constitutively activates transcription factors STAT-3 and NF-kappa B via oxidative stress. Molecular and cellular biology 21: 7721-7730

Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98: 115-124

Xia L, Tian D, Huang W, Zhu H, Wang J, Zhang Y, Hu H, Nie Y, Fan D, Wu K (2012) Upregulation of IL-23 expression in patients with chronic hepatitis B is mediated by the HBx/ERK/NF-kappaB pathway. Journal of immunology 188: 753-764

Xiao F, Yu J, Liu B, Guo Y, Li K, Deng J, Zhang J, Wang C, Chen S, Du Y, Lu Y, Xiao Y, Zhang Z, Guo F (2014) A novel function of microRNA 130a-3p in hepatic insulin sensitivity and liver steatosis. Diabetes 63: 2631-2642

Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, Huang Y, Qi Y, Peng B, Wang H, Fu L, Song M, Chen P, Gao W, Ren B, Sun Y, Cai T, Feng X, Sui J, Li W (2012) Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus. eLife 1: e00049

Yang CC, Huang EY, Li HC, Su PY, Shih C (2014) Nuclear Export of Human Hepatitis B Virus Core Protein and Pregenomic RNA Depends on the Cellular NXF1-p15 Machinery. PloS one 9: e106683

Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM (2001) Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413: 131-138

Yoon S, Jung J, Kim T, Park S, Chwae YJ, Shin HJ, Kim K (2011) Adiponectin, a downstream target gene of peroxisome proliferator-activated receptor gamma, controls hepatitis B virus replication. Virology 409: 290-298
Yu X, Mertz JE (2001) Critical roles of nuclear receptor response elements in replication of hepatitis B virus. Journal of virology 75: 11354-11364

Zhang GL, Li YX, Zheng SQ, Liu M, Li X, Tang H (2010) Suppression of hepatitis B virus replication by microRNA-199a-3p and microRNA-210. Antiviral research 88: 169-175

Zhang J, Wu H, Li P, Zhao Y, Liu M, Tang H (2014) NF-kappaB-modulated miR-130a targets TNF-alpha in cervical cancer cells. Journal of translational medicine 12: 155

Zhang X, Daucher M, Armistead D, Russell R, Kottilil S (2013) MicroRNA expression profiling in HCV-infected human hepatoma cells identifies potential anti-viral targets induced by interferon-alpha. PloS one 8: e55733

Zhou Y, Wang S, Ma JW, Lei Z, Zhu HF, Lei P, Yang ZS, Zhang B, Yao XX, Shi C, Sun LF, Wu XW, Ning Q, Shen GX, Huang B (2010) Hepatitis B virus protein X-induced expression of the CXC chemokine IP-10 is mediated through activation of NF-kappaB and increases migration of leukocytes. The Journal of biological chemistry 285: 12159-12168


QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top