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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 鄭永銘 | |
dc.contributor.author | Ya-Yun Chang | en |
dc.contributor.author | 張雅雲 | zh_TW |
dc.date.accessioned | 2021-06-15T12:51:07Z | - |
dc.date.available | 2021-08-26 | |
dc.date.copyright | 2016-08-26 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-07-20 | |
dc.identifier.citation | 1. Viggiano D, Ianiro G, Vanella G, et al. Gut barrier in health and disease: focus on childhood. Eur Rev Med Pharmacol Sci 2015, 19:1077-85.
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LI-Cadherin–mediated Cell–Cell Adhesion Does Not Require Cytoplasmic Interactions. The Journal of Cell Biology 1997, 136:1109-21. 33. Wendeler MW, Drenckhahn D, Gessner R, et al. Intestinal LI-cadherin acts as a Ca2+-dependent adhesion switch. J Mol Biol 2007, 370:220-30. 34. Gessner R, Tauber R. Intestinal Cell Adhesion Molecules: Liver-Intestine Cadherin. Annals of the New York Academy of Sciences 2006, 915:136-43. 35. Su MC, Yuan RH, Lin CY, et al. Cadherin-17 is a useful diagnostic marker for adenocarcinomas of the digestive system. Mod Pathol 2008, 21:1379-86. 36. Baumgartner W, Wendeler MW, Weth A, et al. Heterotypic trans-interaction of LI- and E-cadherin and their localization in plasmalemmal microdomains. J Mol Biol 2008, 378:44-54. 37. Kreft B, Berndorff D, Bottinger A, et al. LI-cadherin-mediated cell-cell adhesion does not require cytoplasmic interactions. J Cell Biol 1997, 136:1109-21. 38. Ahl M, Weth A, Walcher S, et al. 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Expression of liver-intestine cadherin and its possible interaction with galectin-3 in ductal adenocarcinoma of the pancreas. Cancer Sci 2003, 94:425-30. 50. Lin Z, Zhang C, Zhang M, et al. Targeting cadherin-17 inactivates Ras/Raf/MEK/ERK signaling and inhibits cell proliferation in gastric cancer. PloS one 2014, 9:e85296. 51. Qiu HB, Zhang LY, Ren C, et al. Targeting CDH17 suppresses tumor progression in gastric cancer by downregulating Wnt/beta-catenin signaling. PloS one 2013, 8:e56959. 52. Wang J, Kang WM, Yu JC, et al. Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFkappaB signaling pathway. Cancer Biol Ther 2013, 14:262-70. 53. Pu J, Frescas D, Zhang B, et al. Utilization of TALEN and CRISPR/Cas9 technologies for gene targeting and modification. Exp Biol Med (Maywood) 2015, 240:1065-70. 54. Sung YH, Baek IJ, Kim DH, et al. Knockout mice created by TALEN-mediated gene targeting. Nat Biotechnol 2013, 31:23-4. 55. Reyon D, Tsai SQ, Khayter C, et al. FLASH assembly of TALENs for high-throughput genome editing. Nat Biotechnol 2012, 30:460-5. 56. Wang L, Srinivasan S, Theiss AL, et al. Interleukin-6 induces keratin expression in intestinal epithelial cells: potential role of keratin-8 in interleukin-6-induced barrier function alterations. The Journal of biological chemistry 2007, 282:8219-27. 57. Chen C, Wang P, Su Q, et al. Myosin light chain kinase mediates intestinal barrier disruption following burn injury. PloS one 2012, 7:e34946. 58. Cooper HS, Murthy SN, Shah RS, et al. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest 1993, 69:238-49. 59. Dieleman LA, Palmen MJ, Akol H, et al. Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 1998, 114:385-91. 60. Kuo WT, Lee TC, Yang HY, et al. LPS receptor subunits have antagonistic roles in epithelial apoptosis and colonic carcinogenesis. Cell Death Differ 2015, 22:1590-604. 61. Koliaraki V, Pasparakis M, Kollias G. IKKbeta in intestinal mesenchymal cells promotes initiation of colitis-associated cancer. J Exp Med 2015, 212:2235-51. 62. Uronis JM, Muhlbauer M, Herfarth HH, et al. Modulation of the intestinal microbiota alters colitis-associated colorectal cancer susceptibility. PloS one 2009, 4:e6026. 63. Nishisho I, Nakamura Y, Miyoshi Y, et al. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991, 253:665-9. 64. Jeanes A, Gottardi CJ, Yap AS. Cadherins and cancer: how does cadherin dysfunction promote tumor progression? Oncogene 2008, 27:6920-9. 65. Tanaka H, Takechi M, Kiyonari H, et al. Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice. Gut 2015, 64:1529-38. 66. Tanaka-Okamoto M, Hori K, Ishizaki H, et al. Involvement of afadin in barrier function and homeostasis of mouse intestinal epithelia. Journal of cell science 2011, 124:2231-40. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/50658 | - |
dc.description.abstract | 有許多微生物以及各種的營養物質每天和我們的腸胃道進行接觸。而腸道屏障是一個具有功能的構造,它保護我們免受病原體的入侵、調節營養物質的吸收並且維護腸道免疫黏膜系統的平衡。因此維持一個健康的腸道屏障是非常重要的。腸道上皮細胞接合物複合體包含連接複合體(AJ)以及緊密複合體(TJ)。當接合物複合體失調時,會造成腸道上皮細胞調節腸道通透性的功能喪失,這在許多疾病中扮演著重要的角色。鈣黏著蛋白(Cadherin)是一種跨膜醣蛋白(transmembrane glycoprotein),會去調節由鈣作為傳導物質的連接,並且是連接複合體(AJ)著主要組成之一。鈣黏著蛋白17(Cadherin-17)是一種腸道專一性表現的鈣黏著蛋白。我們利用類轉錄激活因子活化物核酸酶技術(TALEN)來生產鈣黏著蛋白17的基因剔除小鼠。我們發現在鈣黏著蛋白17的基因剔除小鼠中,在絨毛的長度以及增值比率上並沒有變化。且透過電子顯微鏡觀察,鈣黏著蛋白17的基因剔除小鼠和正常小鼠在腸道上皮細胞之間的細胞複合體並沒有不同。然而對於鈣黏著蛋白17的基因剔除小鼠,不論是在體內還是體外的腸道通透性實驗,相較於正常小鼠,通透性都有顯著的增加。而且鈣黏著蛋白17的基因剔除小鼠相較於正常小鼠,牠對於由葡聚糖硫酸钠(DSS)所誘導的結腸炎(colitis)也更為敏感。更為重要的是我們可以在鈣黏著蛋白17的基因剔除小鼠腸道中發現自發性生長的腺瘤(adenoma)。在AOM/DSS小鼠腸道致癌的實驗中,我們也發現鈣黏著蛋白17的基因剔除小鼠有較多,較大,和較惡性的腸道腫瘤。 | zh_TW |
dc.description.abstract | A wide variety of microorganisms and nutrient compounds contact with the gastrointestinal tract every day. The gut barrier is the functional unit required for protection from pathogen, regulation of nutrient absorption, and maintenance of the balance of gut mucosal immune system. The maintenance of a healthy intestinal barrier is very important. The intestinal epithelial cell junctional complexes include adherens junctions (AJs) and tight junctions(TJs). The epithelial permeability dysfunction caused by derangement in the junctional complex plays importance roles in many diseases. Cadherins are transmembrane glycoproteins that mediate Ca2+-dependent adhesion between adjacent cells and are the major components of AJ.Cadherin-17is an intestine-specific cadherin. We generated a knockout mice model of cadherin-17 using the TALEN technique. We found that the length of villus of the cdh17-/-mice was no changed. The proliferation rate was also not changed in cdh17-/- mice. Electomicroscopy showed the cell junction between intestinal epithelial cells did not different between the cdh17-/-mice and wild type mice. Cdh17-/- mice showed increased permeability of small intestinal wall in vitro and in vivo permeability assays. Cdh17-/-mice were also more susceptible to DSS-induced colitis. Spontaneous adenoma formation was found in cdh17-/- mice. In AOM/DSS colitis-induced intestinal carcinogenesis model, cdh17-/- mice had more number, larger, and more malignant tumor than the wild type mice | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T12:51:07Z (GMT). No. of bitstreams: 1 ntu-105-R02444005-1.pdf: 2517906 bytes, checksum: 9ebbe0fc5dd2ca1163ce4e03b6dfa1d3 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 口試委員審定書......................................... i
致謝.................................................. ii 中文摘要.............................................. iii Abstract.............................................. iv Index................................................. vi I.Introduction..........................................1 1.1.Gut barrier functional unit in health and disease...1 1.2.The junctional complexes are important to maintain intestinal homeostasis, morphogenesis and prevention of disease.................................................1 1.3.The cadherin superfamily members are transmembranous glycoproteins mediating Ca2+-dependent cell adhesion................................................3 1.4.Cadherin-17 is an intestine-specific cadherin.......3 1.5.The role of cadherin-17 expression in tumorigenesis...........................................5 1.6.Specific Aims.......................................6 II.Materials and Methods................................8 2.1.Mice................................................8 2.2.Histological examination............................9 2.3.Immunohistochemical staining.......................10 2.4.Western blot.......................................10 2.5.Electromicroscopy..................................11 2.6.In vitro permeability measurement..................12 2.7.In vivo permeability assay.........................13 2.8.Induction and assessment of mouse colitis..........13 2.9.Spontaneous tumor formation........................14 2.10.Azoxymethane (AOM)/DSS colitis-associated colorectal cancer model...........................................15 2.11.ApcMin mice model.................................16 III.Results............................................17 3.1.Generation of a knockout mice model of cadherin-17.....................................................17 3.2.The architecture of the intestinal epithelium did not change in cadherin17-/- mice...........................17 3.3.Increased epithelial permeability of the small intestines in cdh17-/- mice............................18 3.4.Cadherin-17-/- mice had enhanced susceptibility to treatment with dextran sulfate sodium..................19 3.5.Spontaneous tumor formation in the cdh17-/- mice .......................................................20 3.6.The cadherin-17-/- mice were more susceptible to AOM/DSS colitis-associated tumorigenesis...............21 IV.Discussion.........................................23 4.1.Different functions of E-cadherin and cadherin-17 .......................................................23 4.2.Different phenotype of loss of tight junction and adherens junction proteins.............................23 4.3.Cadherin-17 knockout mice are more sensitive to DSS treatment.........................................24 4.4.The cadherin-17 is a candidate tumor suppressor .......................................................24 4.5.The biological function of cadherin-17.............25 V.Figures.............................................26 Figure 1.The knockout mice model of cadherin-17........26 Figure 2.The loss of expression of cadherin-17 in the knockout mice..........................................27 Figure 3.Histology analysis of cadherin-17-/- mice.....28 Figure 4.The PCNA immunostaining of cadherin-17-/- mice and wild type mice.....................................30 Figure 5.The width of intercellular space was not changed in the intestinal epithelial cells of cdh17-/- mice...................................................31 Figure 6.Ussing chamber experiment showed cdh17-/- mice had enhanced paracellular permeability for FITC-dextran. .......................................................33 Figure 7.The in vivo permeability assay showed cdh17-/- had enhanced paracellular permeability.................35 Figure 8.The cdh17-/- mice had enhanced susceptibility to DSS-induced epithelial injury in 2.5% DSS treatment experiment.............................................36 Figure 9.The cdh17-/- mice had enhanced susceptibility to DSS-induced epithelial injury in 2% DSS treatment......38 Figure 10.Differences of sensitivity to DSS treatment between the wild type and cdh17-/- mice................39 Figure 11.The length of cecum and colon of the cdh17-/- mice was not shortened, but the cdh17-/- mice had severer colitis than wild type mice............................40 Figure 12.The small intestinal adenoma in cdh17-/- mice .......................................................42 Figure 13.An intestinal adenoma was found in another 6-month-old female cdh17-/- mice.........................43 Figure 14.The cdh17-/- enhanced colitis-associated tumorigenesis..........................................44 VI.References...........................................46 | |
dc.language.iso | en | |
dc.title | cadherin-17在腸道的屏障功能以及腸道致癌中所扮演的角色 | zh_TW |
dc.title | The role of cadherin-17 in barrier function of intestine and intestinal carcinogenesis | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 余佳慧,倪衍玄 | |
dc.subject.keyword | 連接複合體,鈣黏著蛋白17,基因剔除小鼠,結腸炎,結直腸腫瘤, | zh_TW |
dc.subject.keyword | adherens junction,Cadherin-17,knockout mice,colitis,colorectal neoplasm, | en |
dc.relation.page | 54 | |
dc.identifier.doi | 10.6342/NTU201600998 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-07-20 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 病理學研究所 | zh_TW |
顯示於系所單位: | 病理學科所 |
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