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研究生:謝名凱
研究生(外文):Ming-KaiHsieh
論文名稱:透明質酸對於發炎細胞基因表現的影響
論文名稱(外文):Effects of Hyaluronan on the Gene Expression of Inflammatory Cells
指導教授:黃玲惠
指導教授(外文):Lynn L.H. Huang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:生物科技研究所碩博士班
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:94
中文關鍵詞:傷口癒合生長因子細胞激素透明質酸
外文關鍵詞:Wound HealingGrowth factorCytokineHyaluronan
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傷口癒合為人體受傷後皮膚組織再生的過程,由非常複雜的生理機制調控。許多研究指出,傷口初期的發炎反應是啟動傷口癒合的關鍵,發炎細胞在其中扮演相當重要的角色,除了進行病原菌的清除,也會分泌生長因子及細胞激素來加強發炎並活化組織細胞的增生、分化和細胞外基質的生合成。研究顯示,透明質酸在傷口癒合中能防止發炎反應的過度發生且有促進傷口癒合的功能。因透明質酸具有高度的生物相容性、可分解吸收性、低免疫性及保水性,所以常被使用於傷口敷材的研發上。至於透明質酸對於發炎細胞的影響,尤其在基因表現上的影響,目前為止仍沒有相關的研究報導。本研究目的在探討透明質酸對於發炎細胞在增生、趨化及相關基因表現的影響,藉以推論透明質酸促進傷口癒合的機制。結果發現,在不同分子量與不同濃度的透明質酸處理下,中、高分子量(780、1470、2000、2590 kDa)的透明質酸能促進發炎細胞的增生與趨化反應,且增加HB-EGF、FGF-7、PDGF、VEGF、TGF-β、MMP家族等生長因子及細胞激素基因的表現。因此從結果推論,在傷口癒合初期給予透明質酸,可驅使發炎細胞遷移至傷口處,且刺激其增生,並提升發炎細胞在生長因子及細胞激素基因的表現量,進而達到促進傷口癒合的效果。
Wound healing can be divided into the process of coagulation, inflammation, tissue proliferation, and wound remodeling, each stage of the process not only overlap each other, and by the very complex regulation of physiological mechanisms. Known in the early wound healing, the inflammatory cells such as neutrophil and macrophage are playing an important role to eliminate the invader but also trigger the healing process.
By secreting the specific growth factors and cytokines to activate the downstream cell (including fibroblasts, keratinocytes and epidermal cells) proliferation and differentiation, then to promote extracellular matrix synthesis to assist wound healing.
Extracellular matrix components - hyaluronan can prevent the excessively inflammatory response in the wound healing process. Because hyaluronan has a highly biocompatible, biodegradable absorbent, low immunogenicity, and the excellent water retentivity. Often used in the research and development of a wound dressing materials. There are supporting cells to migration and resist the mechanical stress. As regards the influence of hyaluronan for the inflammatory cells, especially in the influence on the gene expression, by far not related to the study reported. So the purpose of this study was to explore hyaluronan for cell proliferation, cell chemotaxis and gene expression and mechanisms in order to infer hyaluronan to promote wound healing.
The results showed that the treatment of the different molecular weights and different concentrations of hyaluronan, the high molecular weight of hyaluronan(780, 910, 1470, 2000, 2590 kDa) can promote the proliferation and chemotaxis of inflammatory cells, and increased HB-EGF, FGF-7, PDGF, VEGF, TGF-β, MMP family (Collagenase, MT-MMP) and other growth factor and cytokine gene expression. We conclude that the early stages of wound healing give extra hyaluronan, by trigger inflammatory cells migrate to the wound, and stimulate their proliferation and inflammatory cells in growth factor and cytokine gene expression, thus achieving promote wound healing. Since we understand the expression profile between extracellular matrix and inflammatory cell, it facilitating future development of related medical products industry to accelerate wound healing and can achieve the effect without scars.

中文摘要 1
Abstract 2
誌謝 3
目錄 4
表目錄 7
圖目錄 8
符號及名詞縮寫 10
一、研究背景與目的 13
1.1 傷口癒合 13
1.1.1 影響傷口癒合之因子 14
1.2 發炎細胞簡介 14
1.2.1 免疫細胞概述 14
1.2.2 發炎細胞與傷口癒合 15
1.3 細胞外基質簡介 15
1.3.1 細胞外基質在傷口癒合之研究 15
1.3.2 透明質酸(hyaluronan)概述 16
1.3.3 透明質酸與發炎反應之關係 17
1.4 生長因子、細胞激素以及基質金屬蛋白酶簡介 18
1.4.1 生長因子(growth factor) 18
1.4.2 細胞激素(cytokine) 19
1.4.3 基質金屬蛋白酶(matrix metalloproteinase,MMP) 20
1.5 研究目的 21
二、研究材料與方法 22
2.1 實驗藥品 22
2.2 實驗儀器與材料 24
2.3 實驗設計 27
2.3.1 發炎細胞之鑑定 27
2.3.2 發炎細胞分析技術之建立 27
2.4 實驗方法 29
2.4.1 發炎細胞之鑑定 29
2.4.2 發炎細胞分析技術建立 31
三、研究結果 41
3.1 實驗結果 41
3.1.1發炎細胞之鑑定 41
3.1.2 發炎細胞分析技術之建立 42
四、討論 50
4.1 實驗討論 50
4.1.1 發炎細胞之增生試驗 50
4.1.2 發炎細胞之基因表現量測定 51
五、參考文獻 78
六、附錄 82
1Beanes, S. R., Dang, C., Soo, C. and Ting, K., Skin repair and scar formation: the central role of TGF-[beta]. Expert Reviews in Molecular Medicine 2004. 5.
2Gurtner, G. C., Werner, S., Barrandon, Y. and Longaker, M. T., Wound repair and regeneration. Nature 2008. 453: 314-321.
3Guo, S. and Dipietro, L. A., Factors affecting wound healing. Journal of dental research 2010. 89: 219-229.
4DiPietro, L. A., Wound healing: the role of the macrophage and other immune cells. Shock 1995. 4: 233-240.
5Park, J. E. and Barbul, A., Understanding the role of immune regulation in wound healing. The American Journal of Surgery 2004. 187: S11-S16.
6Rodero, M. P. and Khosrotehrani, K., Skin wound healing modulation by macrophages. International journal of clinical and experimental pathology 2010. 3: 643-653.
7Necas, J., Bartosikova, L., Brauner, P., Kolar, J., Hyaluronic acid (hyaluronan): a review. Veterinarni Medicina 2008. 53: 397–411.
8Schultz, G. S. and Wysocki, A., Interactions between extracellular matrix and growth factors in wound healing. Wound Repair and Regeneration 2009. 17: 153-162.
9Dechert, T. A., Ducale, A. E., Ward, S. I. and Yager, D. R., Hyaluronan in human acute and chronic dermal wounds. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 2006. 14: 252-258.
10Jiang, D., Liang, J. and Noble, P. W., Hyaluronan in tissue injury and repair. Annual review of cell and developmental biology 2007. 23: 435-461.
11Forrester, J. V. and Lackie, J. M., Effect of hyaluronic acid on neutrophil adhesion. Journal of cell science 1981. 50: 329-344.
12Forrester, J. V. and Wilkinson, P. C., Inhibition of leukocyte locomotion by hyaluronic acid. Journal of cell science 1981. 48: 315-331.
13Nandi, A., Estess, P. and Siegelman, M. H., Hyaluronan anchoring and regulation on the surface of vascular endothelial cells is mediated through the functionally active form of CD44. Journal of Biological Chemistry 2000. 275: 14939-14948.
14Partsch, G., Schwarzer, C., Neumuller, J., Dunky, A., Petera, P., Broll, H., Ittner, G. and Jantsch, S., Modulation of the migration and chemotaxis of PMN cells by hyaluronic acid. Zeitschrift fur Rheumatologie 1989. 48: 123-128.
15Neumann, A., Schinzel, R., Palm, D., Riederer, P. and Munch, G., High molecular weight hyaluronic acid inhibits advanced glycation endproduct-induced NF-kappaB activation and cytokine expression. FEBS letters 1999. 453: 283-287.
16Sezgin, M., Demirel, A. C., Karaca, C., Ortancil, O., Ulkar, G. B., Kanik, A. and Cakci, A., Does hyaluronan affect inflammatory cytokines in knee osteoarthritis? Rheumatology International 2005. 25: 264-269.
17Takahashi, K., Goomer, R. S., Harwood, F., Kubo, T., Hirasawa, Y. and Amiel, D., The effects of hyaluronan on matrix metalloproteinase-3 (MMP-3), interleukin-1beta(IL-1beta), and tissue inhibitor of metalloproteinase-1 (TIMP-1) gene expression during the development of osteoarthritis. Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society 1999. 7: 182-190.
18Yasui, T., Akatsuka, M., Tobetto, K., Hayaishi, M. and Ando, T., The effect of hyaluronan on interleukin-1 alpha-induced prostaglandin E2 production in human osteoarthritic synovial cells. Agents and actions 1992. 37: 155-156.
19Barrientos, S., Stojadinovic, O., Golinko, M. S., Brem, H. and Tomic-Canic, M., Growth factors and cytokines in wound healing. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 2008. 16: 585-601.
20Efron, P. A. and Moldawer, L. L., Cytokines and wound healing: the role of cytokine and anticytokine therapy in the repair response. The Journal of burn care & rehabilitation 2004. 25: 149-160.
21Richard Coico, G. S., Eli Benjamini, Immunology: A Short Course FIFTH EDITION 2003.
22Madlener, M., Parks, W. C. and Werner, S., Matrix metalloproteinases (MMPs) and their physiological inhibitors (TIMPs) are differentially expressed during excisional skin wound repair. Experimental cell research 1998. 242: 201-210.
23Martin, S. J., Bradley, J. G. and Cotter, T. G., HL-60 cells induced to differentiate towards neutrophils subsequently die via apoptosis. Clinical and experimental immunology 1990. 79: 448-453.
24Jiang, D. H., Liang, J. R. and Noble, P. W., Hyaluronan as an Immune Regulator in Human Diseases. Physiological reviews 2011. 91: 221-264.
25Tammi, R. H. and Tammi, M. I., Hyaluronan accumulation in wounded epidermis: a mediator of keratinocyte activation. The Journal of investigative dermatology 2009. 129: 1858-1860.
26Van Epps, H. L., Healing with hyaluronan. The Journal of experimental medicine 2005. 201: 1181.
27Efron, P. A. and Moldawer, L. L., Cytokines and Wound Healing: The Role of Cytokine and Anticytokine Therapy in the Repair Response. Journal of Burn Care & Rehabilitation 2004. 25: 149-160.
28Noble, P. W., Lake, F. R., Henson, P. M. and Riches, D. W., Hyaluronate activation of CD44 induces insulin-like growth factor-1 expression by a tumor necrosis factor-alpha-dependent mechanism in murine macrophages. The Journal of clinical investigation 1993. 91: 2368-2377.
29McKee, C. M., Penno, M. B., Cowman, M., Burdick, M. D., Strieter, R. M., Bao, C. and Noble, P. W., Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. The role of HA size and CD44. The Journal of clinical investigation 1996. 98: 2403-2413.
30Horton, M. R., Burdick, M. D., Strieter, R. M., Bao, C. and Noble, P. W., Regulation of hyaluronan-induced chemokine gene expression by IL-10 and IFN-gamma in mouse macrophages. Journal of immunology 1998. 160: 3023-3030.
31Nakamura, K., Yokohama, S., Yoneda, M., Okamoto, S., Tamaki, Y., Ito, T., Okada, M., Aso, K. and Makino, I., High, but not low, molecular weight hyaluronan prevents T-cell-mediated liver injury by reducing proinflammatory cytokines in mice. Journal of gastroenterology 2004. 39: 346-354.
32Schimizzi, A. L., Massie, J. B., Murphy, M., Perry, A., Kim, C. W., Garfin, S. R. and Akeson, W. H., High-molecular-weight hyaluronan inhibits macrophage proliferation and cytokine release in the early wound of a preclinical postlaminectomy rat model. The spine journal : official journal of the North American Spine Society 2006. 6: 550-556.
33Voelcker, V., Gebhardt, C., Averbeck, M., Saalbach, A., Wolf, V., Weih, F., Sleeman, J., Anderegg, U. and Simon, J., Hyaluronan fragments induce cytokine and metalloprotease upregulation in human melanoma cells in part by signalling via TLR4. Experimental dermatology 2008. 17: 100-107.
34Gao, F., Liu, Y. W., He, Y. Q., Yang, C. X., Wang, Y. Z., Shi, X. X. and Wei, G., Hyaluronan oligosaccharides promote excisional wound healing through enhanced angiogenesis. Matrix Biology 2010. 29: 107-116.
35Galeano, M., Polito, F., Bitto, A., Irrera, N., Campo, G. M., Avenoso, A., Calo, M., Lo Cascio, P., Minutoli, L., Barone, M., Squadrito, F. and Altavilla, D., Systemic administration of high-molecular weight hyaluronan stimulates wound healing in genetically diabetic mice. Biochimica Et Biophysica Acta-Molecular Basis of Disease 2011. 1812: 752-759.
36Diegelmann, R. F. and Evans, M. C., Wound healing: an overview of acute, fibrotic and delayed healing. Frontiers in bioscience : a journal and virtual library 2004. 9: 283-289.
37Park, J., Understanding the role of immune regulation in wound healing. The American Journal of Surgery 2004. 187: S11-S16.

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