請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61188
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 李明學(Ming-Shyue Lee) | |
dc.contributor.author | Chun-Pai Juan | en |
dc.contributor.author | 阮君白 | zh_TW |
dc.date.accessioned | 2021-06-16T10:51:54Z | - |
dc.date.available | 2018-09-24 | |
dc.date.copyright | 2013-09-24 | |
dc.date.issued | 2013 | |
dc.date.submitted | 2013-08-09 | |
dc.identifier.citation | 1. Schneeberger, E.E. and Lynch, R.D. (2004) The tight junction: a multifunctional complex. American journal of physiology. Cell physiology, 286, C1213-1228.
2. Tsukita, S., Furuse, M. and Itoh, M. (2001) Multifunctional strands in tight junctions. Nature reviews. Molecular cell biology, 2, 285-293. 3. Spring, K.R. (1998) Routes and mechanism of fluid transport by epithelia. Annual review of physiology, 60, 105-119. 4. Schneeberger, E.E. and Lynch, R.D. (1992) Structure, function, and regulation of cellular tight junctions. The American journal of physiology, 262, L647-661. 5. Harhaj, N.S. and Antonetti, D.A. (2004) Regulation of tight junctions and loss of barrier function in pathophysiology. The international journal of biochemistry & cell biology, 36, 1206-1237. 6. Laukoetter, M.G., Nava, P. and Nusrat, A. (2008) Role of the intestinal barrier in inflammatory bowel disease. World journal of gastroenterology : WJG, 14, 401-407. 7. Rao, Y.X., Chen, J., Chen, L.L., Gu, W.Z. and Shu, X.L. (2012) [Changes in tight junction protein expression and permeability of colon mucosa in rats with dextran sulfate sodium-induced inflammatory bowel disease]. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics, 14, 976-981. 8. Chiba, H., Kojima, T., Osanai, M. and Sawada, N. (2006) The significance of interferon-gamma-triggered internalization of tight-junction proteins in inflammatory bowel disease. Science's STKE : signal transduction knowledge environment, 2006, pe1. 9. Kooistra, M.R., Dube, N. and Bos, J.L. (2007) Rap1: a key regulator in cell-cell junction formation. Journal of cell science, 120, 17-22. 10. Lynch, R.D., Tkachuk-Ross, L.J., McCormack, J.M., McCarthy, K.M., Rogers, R.A. and Schneeberger, E.E. (1995) Basolateral but not apical application of protease results in a rapid rise of transepithelial electrical resistance and formation of aberrant tight junction strands in MDCK cells. European journal of cell biology, 66, 257-267. 11. Swystun, V., Chen, L., Factor, P., Siroky, B., Bell, P.D. and Matalon, S. (2005) Apical trypsin increases ion transport and resistance by a phospholipase C-dependent rise of Ca2+. American journal of physiology. Lung cellular and molecular physiology, 288, L820-830. 12. Buzza, M.S., Netzel-Arnett, S., Shea-Donohue, T., Zhao, A., Lin, C.Y., List, K., Szabo, R., Fasano, A., Bugge, T.H. and Antalis, T.M. (2010) Membrane-anchored serine protease matriptase regulates epithelial barrier formation and permeability in the intestine. Proceedings of the National Academy of Sciences of the United States of America, 107, 4200-4205. 13. Buzza, M.S., Martin, E.W., Driesbaugh, K.H., Desilets, A., Leduc, R. and Antalis, T.M. (2013) Prostasin is required for matriptase activation in intestinal epithelial cells to regulate closure of the paracellular pathway. The Journal of biological chemistry. 14. Hooper, J.D., Clements, J.A., Quigley, J.P. and Antalis, T.M. (2001) Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. The Journal of biological chemistry, 276, 857-860. 15. Bugge, T.H., Antalis, T.M. and Wu, Q. (2009) Type II transmembrane serine proteases. The Journal of biological chemistry, 284, 23177-23181. 16. Szabo, R. and Bugge, T.H. (2011) Membrane-anchored serine proteases in vertebrate cell and developmental biology. Annual review of cell and developmental biology, 27, 213-235. 17. Takeuchi, T., Harris, J.L., Huang, W., Yan, K.W., Coughlin, S.R. and Craik, C.S. (2000) Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates. The Journal of biological chemistry, 275, 26333-26342. 18. Szabo, R. and Bugge, T.H. (2008) Type II transmembrane serine proteases in development and disease. The international journal of biochemistry & cell biology, 40, 1297-1316. 19. List, K., Haudenschild, C.C., Szabo, R., Chen, W., Wahl, S.M., Swaim, W., Engelholm, L.H., Behrendt, N. and Bugge, T.H. (2002) Matriptase/MT-SP1 is required for postnatal survival, epidermal barrier function, hair follicle development, and thymic homeostasis. Oncogene, 21, 3765-3779. 20. Yuan, X., Zheng, X., Lu, D., Rubin, D.C., Pung, C.Y. and Sadler, J.E. (1998) Structure of murine enterokinase (enteropeptidase) and expression in small intestine during development. The American journal of physiology, 274, G342-349. 21. Paoloni-Giacobino, A., Chen, H., Peitsch, M.C., Rossier, C. and Antonarakis, S.E. (1997) Cloning of the TMPRSS2 gene, which encodes a novel serine protease with transmembrane, LDLRA, and SRCR domains and maps to 21q22.3. Genomics, 44, 309-320. 22. Afar, D.E., Vivanco, I., Hubert, R.S., Kuo, J., Chen, E., Saffran, D.C., Raitano, A.B. and Jakobovits, A. (2001) Catalytic cleavage of the androgen-regulated TMPRSS2 protease results in its secretion by prostate and prostate cancer epithelia. Cancer research, 61, 1686-1692. 23. Chen, Y.W., Lee, M.S., Lucht, A., Chou, F.P., Huang, W., Havighurst, T.C., Kim, K., Wang, J.K., Antalis, T.M., Johnson, M.D. et al. (2010) TMPRSS2, a serine protease expressed in the prostate on the apical surface of luminal epithelial cells and released into semen in prostasomes, is misregulated in prostate cancer cells. The American journal of pathology, 176, 2986-2996. 24. Lin, B., Ferguson, C., White, J.T., Wang, S., Vessella, R., True, L.D., Hood, L. and Nelson, P.S. (1999) Prostate-localized and androgen-regulated expression of the membrane-bound serine protease TMPRSS2. Cancer research, 59, 4180-4184. 25. Tomlins, S.A., Rhodes, D.R., Perner, S., Dhanasekaran, S.M., Mehra, R., Sun, X.W., Varambally, S., Cao, X., Tchinda, J., Kuefer, R. et al. (2005) Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science, 310, 644-648. 26. Ahlers, C.M. and Figg, W.D. (2006) ETS-TMPRSS2 fusion gene products in prostate cancer. Cancer biology & therapy, 5, 254-255. 27. Yu, J., Yu, J., Mani, R.S., Cao, Q., Brenner, C.J., Cao, X., Wang, X., Wu, L., Li, J., Hu, M. et al. (2010) An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression. Cancer cell, 17, 443-454. 28. Takeuchi, T., Shuman, M.A. and Craik, C.S. (1999) Reverse biochemistry: use of macromolecular protease inhibitors to dissect complex biological processes and identify a membrane-type serine protease in epithelial cancer and normal tissue. Proceedings of the National Academy of Sciences of the United States of America, 96, 11054-11061. 29. Tanimoto, H., Underwood, L.J., Wang, Y., Shigemasa, K., Parmley, T.H. and O'Brien, T.J. (2001) Ovarian tumor cells express a transmembrane serine protease: a potential candidate for early diagnosis and therapeutic intervention. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine, 22, 104-114. 30. Cao, J., Cai, X., Zheng, L., Geng, L., Shi, Z., Pao, C.C. and Zheng, S. (1997) Characterization of colorectal-cancer-related cDNA clones obtained by subtractive hybridization screening. Journal of cancer research and clinical oncology, 123, 447-451. 31. Lin, C.Y., Anders, J., Johnson, M., Sang, Q.A. and Dickson, R.B. (1999) Molecular cloning of cDNA for matriptase, a matrix-degrading serine protease with trypsin-like activity. The Journal of biological chemistry, 274, 18231-18236. 32. MS, L. (2006) Matrix-degrading Type II transmembrane serine protease matriptase: its role in cancer development and malignancy. Journal of Cancer Molecules, 5. 33. Kim, C., Cho, Y., Kang, C.H., Kim, M.G., Lee, H., Cho, E.G. and Park, D. (2005) Filamin is essential for shedding of the transmembrane serine protease, epithin. EMBO reports, 6, 1045-1051. 34. Oberst, M.D., Chen, L.Y., Kiyomiya, K., Williams, C.A., Lee, M.S., Johnson, M.D., Dickson, R.B. and Lin, C.Y. (2005) HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease. American journal of physiology. Cell physiology, 289, C462-470. 35. Cho, E.G., Schwartz, R.H. and Kim, M.G. (2005) Shedding of membrane epithin is blocked without LDLRA4 and its protease activation site. Biochemical and biophysical research communications, 327, 328-334. 36. Oberst MD, C.L., Kiyomiya K, Williams CA, Lee MS, Johnson MD, Dickson RB, Lin CY. . (2005) HAI-1 regulates activation and expression of matriptase, a membrane-bound serine protease. Am J Physiol Cell Physiol, 289, 8. 37. Benaud, C., Dickson, R.B. and Lin, C.Y. (2001) Regulation of the activity of matriptase on epithelial cell surfaces by a blood-derived factor. European journal of biochemistry / FEBS, 268, 1439-1447. 38. Uhland, K. (2006) Matriptase and its putative role in cancer. Cellular and molecular life sciences : CMLS, 63, 2968-2978. 39. Kiyomiya, K., Lee, M.S., Tseng, I.C., Zuo, H., Barndt, R.J., Johnson, M.D., Dickson, R.B. and Lin, C.Y. (2006) Matriptase activation and shedding with HAI-1 is induced by steroid sex hormones in human prostate cancer cells, but not in breast cancer cells. American journal of physiology. Cell physiology, 291, C40-49. 40. Chen, Y.W., Wang, J.K., Chou, F.P., Chen, C.Y., Rorke, E.A., Chen, L.M., Chai, K.X., Eckert, R.L., Johnson, M.D. and Lin, C.Y. (2010) Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation. The Journal of biological chemistry, 285, 31755-31762. 41. Bugge, T.H., List, K. and Szabo, R. (2007) Matriptase-dependent cell surface proteolysis in epithelial development and pathogenesis. Frontiers in bioscience : a journal and virtual library, 12, 5060-5070. 42. List, K., Kosa, P., Szabo, R., Bey, A.L., Wang, C.B., Molinolo, A. and Bugge, T.H. (2009) Epithelial integrity is maintained by a matriptase-dependent proteolytic pathway. The American journal of pathology, 175, 1453-1463. 43. Buzza, M.S., Martin, E.W., Driesbaugh, K.H., Desilets, A., Leduc, R. and Antalis, T.M. (2013) Prostasin is required for matriptase activation in intestinal epithelial cells to regulate closure of the paracellular pathway. The Journal of biological chemistry, 288, 10328-10337. 44. Fogh, J., Fogh, J.M. and Orfeo, T. (1977) One hundred and twenty-seven cultured human tumor cell lines producing tumors in nude mice. Journal of the National Cancer Institute, 59, 221-226. 45. Hidalgo, I.J., Raub, T.J. and Borchardt, R.T. (1989) Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology, 96, 736-749. 46. Gaush, C.R., Hard, W.L. and Smith, T.F. (1966) Characterization of an established line of canine kidney cells (MDCK). Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine, 122, 931-935. 47. Fanning, A.S., Mitic, L.L. and Anderson, J.M. (1999) Transmembrane proteins in the tight junction barrier. Journal of the American Society of Nephrology : JASN, 10, 1337-1345. 48. Nusrat, A., Turner, J.R. and Madara, J.L. (2000) Molecular physiology and pathophysiology of tight junctions. IV. Regulation of tight junctions by extracellular stimuli: nutrients, cytokines, and immune cells. American journal of physiology. Gastrointestinal and liver physiology, 279, G851-857. 49. Nusrat, A., Parkos, C.A., Verkade, P., Foley, C.S., Liang, T.W., Innis-Whitehouse, W., Eastburn, K.K. and Madara, J.L. (2000) Tight junctions are membrane microdomains. Journal of cell science, 113 ( Pt 10), 1771-1781. 50. Anderson, J.M., Van Itallie, C.M., Peterson, M.D., Stevenson, B.R., Carew, E.A. and Mooseker, M.S. (1989) ZO-1 mRNA and protein expression during tight junction assembly in Caco-2 cells. The Journal of cell biology, 109, 1047-1056. 51. Leyvraz, C., Charles, R.P., Rubera, I., Guitard, M., Rotman, S., Breiden, B., Sandhoff, K. and Hummler, E. (2005) The epidermal barrier function is dependent on the serine protease CAP1/Prss8. The Journal of cell biology, 170, 487-496. 52. Miller, G.S. and List, K. (2013) The matriptase-prostasin proteolytic cascade in epithelial development and pathology. Cell and tissue research, 351, 245-253. 53. Friis, S., Sales, K.U., Godiksen, S., Peters, D.E., Lin, C.Y., Vogel, L.K. and Bugge, T.H. (2013) A matriptase-prostasin reciprocal zymogen activation complex with unique features: prostasin as a non-enzymatic co-factor for matriptase activation. The Journal of biological chemistry. 54. Balcarova-Stander, J., Pfeiffer, S.E., Fuller, S.D. and Simons, K. (1984) Development of cell surface polarity in the epithelial Madin-Darby canine kidney (MDCK) cell line. The EMBO journal, 3, 2687-2694. 55. Saier, M.H., Jr. (1981) Growth and differentiated properties of a kidney epithelial cell line (MDCK). The American journal of physiology, 240, C106-109. 56. Kim, T.S., Heinlein, C., Hackman, R.C. and Nelson, P.S. (2006) Phenotypic analysis of mice lacking the Tmprss2-encoded protease. Molecular and cellular biology, 26, 965-975. 57. Hung, R.J., Hsu Ia, W., Dreiling, J.L., Lee, M.J., Williams, C.A., Oberst, M.D., Dickson, R.B. and Lin, C.Y. (2004) Assembly of adherens junctions is required for sphingosine 1-phosphate-induced matriptase accumulation and activation at mammary epithelial cell-cell contacts. American journal of physiology. Cell physiology, 286, C1159-1169. 58. Tsuzuki, S., Murai, N., Miyake, Y., Inouye, K., Hirayasu, H., Iwanaga, T. and Fushiki, T. (2005) Evidence for the occurrence of membrane-type serine protease 1/matriptase on the basolateral sides of enterocytes. The Biochemical journal, 388, 679-687. 59. Godiksen, S., Selzer-Plon, J., Pedersen, E.D., Abell, K., Rasmussen, H.B., Szabo, R., Bugge, T.H. and Vogel, L.K. (2008) Hepatocyte growth factor activator inhibitor-1 has a complex subcellular itinerary. The Biochemical journal, 413, 251-259. 60. Satomi, S., Yamasaki, Y., Tsuzuki, S., Hitomi, Y., Iwanaga, T. and Fushiki, T. (2001) A role for membrane-type serine protease (MT-SP1) in intestinal epithelial turnover. Biochemical and biophysical research communications, 287, 995-1002. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/61188 | - |
dc.description.abstract | 嵌膜絲胺酸蛋白酶 (Transmembrane serine protease) 對於組織恆定性以及緊密連結 (Tight junction) 的形成扮演著重要的角色。近年來,第二型嵌膜絲胺酸蛋白酶家族 (TTPSs) 中的成員,第二型嵌膜蛋白酶 (TMPRSS2) 受到越來越多的關注,因其表達量和攝護腺癌之進程有高度相關性。在一些組織例如:攝護腺及結腸都會選擇性地表達TMPRSS2。然而,TMPRSS2的生理功能及其受質至今仍待研究。實驗室過去的研究指出TMPRSS2會誘發TTSP中的另一個成員,間質蛋白酶 (Matriptase) ,在攝護腺癌細胞中的活化。由於最近的報導指出Matriptase可以調控腸道上皮細胞之Tight junction的形成及其屏障通透性。為了進一步探討TMPRSS2是否在Tight junction的形成中扮演角色?我使用結腸癌細胞 (Caco-2) 作為細胞分化模式,並觀察到此細胞在其分化過程中,TMPRSS2及Matriptase之蛋白表現量,都會隨之增加。當過量表達TMPRSS2,發現此蛋白酶可降低Caco-2細胞的離子通透性,促進屏障功能,且不會影響細胞生長。進一步的研究結果顯示,減弱TMPRSS2之表現量,會降低Matriptase的活化程度但不影響其基因表達量。在過量表達TMPRSS2的細胞中,從共軛焦顯微鏡影像顯示出TMPRSS2,ZO-1及Matriptase共同坐落在Tight junction的區域。進一步的研究發現,當降低TMPRSS2之表現量會削弱ZO-1, occludin, 及claudin-1等Tight junction蛋白質分佈在分化的細胞膜上的量。綜合以上結果,TMPRSS2可促進Tight junction之形成並影響離子通透性,此作用可能是藉由活化Matriptase而達成。因此,本研究成果建議TMPRSS2扮演角色參與調控表皮細胞緊密連結及分化細胞的通透性。 | zh_TW |
dc.description.abstract | Pericellular serine proteases have an important role in tissue homeostasis and tight junction formation. Recently, type II transmembrane serine protease (TTSP) TMPRSS2 has received increasing attention because its expression level is correlated with prostate cancer progression. Several tissues such as prostate and colon also selectively express this protease. However, the biological function and substrate(s) of TMPRSS2 are still unclear. Our preliminary data show that TMPRSS2 can induce the activation of matriptase, another member of TTSP, in prostate cancer cells. Since recent studies have shown that matriptase can regulate intestinal tight junction formation and permeability, we then hypothesized that TMPRSS2 exhibited a role in the tight junction formation of colorectal cells and was crucial for barrier function and permeability. To further investigate the role of TMPRSS2 in tight junction formation, the protein levels of TMPRSS2 and matriptase were examined during the Caco-2 differentiation, and both proteins were increased during the period of cell differentiation. It was observed that TMPRSS2 overexpression in Caco-2 cells decreased iron permeability and increased barrier function during cell differentiation, which were independent of cell growth. Moreover, knockdown of TMPRSS2 reduced the activated level of matriptase in Caco-2 cells. In TMPRSS2-overexpressing Caco-2 cells, the confocal images indicated that TMPRSS2 may co-localize with ZO-1 and matriptase in the TJ region. In addition, TMPRSS2 silencing resulted in the down-regulation of ZO-1, occludin, and claudin-1 in the insoluble membrane fraction of polarized Caco-2 cells. The data together indicate that TMPRSS2 can promote TJ formation and may be via the regulation of matriptase, and suggest that TMPRSS2 plays roles in modulating the TJ formation and permeability of epithelial cells. | en |
dc.description.provenance | Made available in DSpace on 2021-06-16T10:51:54Z (GMT). No. of bitstreams: 1 ntu-102-R00442002-1.pdf: 9654936 bytes, checksum: a1d46b8ddfec933a8967f3e6ef3be21a (MD5) Previous issue date: 2013 | en |
dc.description.tableofcontents | CONTENTS
致謝 I 摘要 III Abstract IV Chapter 1. Introduction 1 1.1 Tight junction 2 1.2 Type II transmembrane serine protease 4 1.3 TMPRSS2 5 1.4 Matriptase 6 1.5 Research motivation 8 Chapter 2. Materials and Methods 10 2.1 Materials 11 2.2 Methods 14 Chapter 3. Results 24 3.1 Protein levels of TMPRSS2, matriptase, HAI-1, and prostasin increased with TEER values during the differentiation of Caco-2 cells. 25 3.2 The gene expression levels of TMPRSS2, matriptase, HAI-1, and prostasin increased during the differentiation of Caco-2 cells. 26 3.3 TMPRSS2 was involved in tight junction formation during Caco-2 cell differentiation. 27 3.4 TMPRSS2 overexpression enhanced barrier formation by increasing the TEER and accelerating the TEER reaching to the plateau during the differentiation program of Caco-2 cells. 28 3.5 Examination of TMPRSS2 role in Caco-2 cell growth. 29 3.6 Role of TMPRSS2 in the expression of matriptase in Caco-2 cells. 29 3.7 Effects of TMPRSS2 overexpression on the TEER of MDCK cells 30 3.8 Subcellular localization of TMPRSS2, ZO-1, E-cadherin and matriptase in polarized Caco-2 cells. 31 3.9 Roles of TMPRSS2 in the subcellular distributions of ZO-1, occludin and claudin-1 proteins in Caco-2 cells. 31 3.10 Effects of TMPRSS2 overexpression on the subcellular distributions of tight junction proteins in Caco-2 cells. 32 Chapter 4. Discussion 34 Chapter 5. Figures 39 Chapter 6. References 62 | |
dc.language.iso | en | |
dc.title | 探討第二型嵌膜蛋白酶參與大腸腺癌細胞間緊密連結的形成 | zh_TW |
dc.title | Involvement of TMPRSS2 in tight junction formation of
Caco-2 cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 101-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 李明亭(Ming-Ting Lee),黃祥博,余佳慧 | |
dc.subject.keyword | 第二型嵌膜蛋白酶,緊密連結,第一型細胞間質蛋白酶,上皮細胞,通透性, | zh_TW |
dc.subject.keyword | TMPRSS2,tight junction,matriptase,epithelial cells and ion permeability, | en |
dc.relation.page | 67 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2013-08-09 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
顯示於系所單位: | 生物化學暨分子生物學科研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-102-1.pdf 目前未授權公開取用 | 9.43 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。