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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 | 郭彥彬 | |
dc.contributor.author | Kai-Yuan Jheng | en |
dc.contributor.author | 鄭凱元 | zh_TW |
dc.date.accessioned | 2021-06-08T03:28:42Z | - |
dc.date.copyright | 2019-08-26 | |
dc.date.issued | 2019 | |
dc.date.submitted | 2019-08-17 | |
dc.identifier.citation | 1. Beaumont J, Chesterman J, Kellett M, Durey K. Gingival overgrowth: Part 1: aetiology and clinical diagnosis. British dental journal, 222: 85-91, 2017.
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The possible potential therapeutic targets for drug induced gingival overgrowth. Mediators of inflammation, 2013: 639468, 2013. 45. Coletta RD, Graner E. Hereditary gingival fibromatosis: a systematic review. Journal of periodontology, 77: 753-764, 2006. 46. Mead AL, Wong TT, Cordeiro MF, Anderson IK, Khaw PT. Evaluation of anti-TGF-beta2 antibody as a new postoperative anti-scarring agent in glaucoma surgery. Investigative ophthalmology & visual science, 44: 3394-3401, 2003. 47. Garg K, Corona BT, Walters TJ. Therapeutic strategies for preventing skeletal muscle fibrosis after injury. Frontiers in pharmacology, 6: 87, 2015. 48. Yamada M, Kuwano K, Maeyama T, et al. Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis. Journal of clinical pathology, 60: 916-920, 2007. 49. Kondo T, Takemura G, Kosai K, et al. 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Fibroblast-specific inhibition of TGF-beta1 signaling attenuates lung and tumor fibrosis. The Journal of clinical investigation, 127: 3675-3688, 2017. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/21207 | - |
dc.description.abstract | 實驗目的和背景:
環孢素(Cyclosporin A)是一種常用在器官移植患者上的免疫抑制藥物,大約有七成服用此藥的病人會產生牙齦過度增生(Gingival overgrowth,GO)的副作用,進而影響到說話、吞嚥、咀嚼、口腔衛生、美觀等等,影響生活品質。轉化生長因子-β(Transforming growth factor,TGF-β) 在牙齦腫大的致病機轉中扮演著主要的角色,先前的研究中發現環孢菌素可經由TGF-β傳導路徑誘發上皮-間質轉換(epithelial-mesenchymal transition,EMT)現象,而使患者牙齦增生。其中離氨基氧化酶樣蛋白2 (Lysyl Oxidase-like protein 2, LOXL-2):除催化膠原蛋白與彈性纖維的交叉共價鍵結(cross-linking)外,在一些研究中指出和EMT現象有關連。本研究期望能更加了解環孢素是否經由LOXL-2誘導人類牙齦上皮細胞產生EMT。 實驗方法: 本研究利用西方墨點法來檢測環孢素-A以及不同抑制劑處理後人類牙齦上皮細胞OECM-1 及 Ca9-22 之LOXL-2的表現以及EMT 標識蛋白Slug及E-cadherin的變化。 實驗結果: 於 OECM-1 及 Ca9-22 細胞加入環孢素素處理後,其 LOXL-2 的表現量隨之增加,OECM-1 細胞在4小時後達到最高值;CA9-22 細胞是在6小時後達到最高值。前處理TGF-β 中和抗體 (20μg/ml)、ALK5 抑制劑SB431542 (20μg/ml)、Smad-3 抑制劑SIS3 (5 μg/ml),可以抑制OECM-1及CA9-22細胞受環孢素誘導的LOXL-2表現。顯示環孢素是經由TGF-β訊息傳導路徑誘導 OECM-1 及 CA9-22 之LOXL-2 的表現。前處理LOXL-2 的抑制劑 BAPN,可以顯著的抑制環孢素誘導的OECM-1 及 Ca9-22細胞上皮-間質轉換標識蛋白Slug的表現增加及E-cadherin的減少。顯示LOXL-2在Cyclosporin A誘導的EMT扮演重要的角色。 結論: 環孢素經由TGF-β及LOXL-2誘導EMT的產生。 | zh_TW |
dc.description.abstract | Objectives:
Cyclosporin A (CsA) is an immunosuppressive drug commonly used in organ transplant patients. Approximately 70% of the patients show gingival overgrowth (GO). Transforming growth factor (TGF-β) plays a major role in the GO. Previous studies have found that Cyclosporin A can induce epithelial-mesenchymal transition (EMT) via TGF-β signaling pathway, which then plays important roles in the pathogenesis of GO. Lysyl oxidase-like protein 2 (LOXL-2) : catalyzes the cross-linking of collagen and elastin to maintain the rigidity and stability of the extracellular matrix protein. Previous studies have shown LOXL-2 plays important roles in EMT. This study investigated the signaling pathways involved in the CsA-induced EMT. Material and Methods: Western blotting was used to examine the levels of LOXL-2 protein and the EMT marker protein E-cadherin and Slug in human gingival epithelial OECM-1 and Ca9-22 cells after treatment with CsA and various inhibitors. Results: CsA induced LOXL-2 in OECM-1 and Ca9-22 cells in a dose- and time- dependent manner. Pretreatment with TGF-β neutralizing antibody, ALK5 inhibitor SB431542 and Smad-3 inhibitor SIS3 almost completely inhibit cyclosporin A-induced LOXL-2 expression in OECM-1 and CA9-22 cells. These results suggest that CsA-induced LOXL-2 expression in gingival epithelial cells is mediated through TGFβ1 signaling. Pretreatment with LOXL-2 inhibitor BAPN significantly reduced CsA-induced Slug protein levels and reversed CsA-reduced E-cadherin expression in OECM-1 and CA9-22 cells. Conclusion: Cyclosporin A induced EMT through TGFβ signaling and LOXL-2 protein expression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-08T03:28:42Z (GMT). No. of bitstreams: 1 ntu-108-R05422018-1.pdf: 1666448 bytes, checksum: 311690c53f9bd18cd573133e6847990b (MD5) Previous issue date: 2019 | en |
dc.description.tableofcontents | 謝誌 i
中文摘要 ii Abstract iii 目錄 iv 導論 1 第一節 牙齦過度增生 1 1-1 牙齦過度增生 1 1-2 牙齦過度增生的流行病學 2 1-3 牙齦過度增生的致病機制 3 1-4 牙齦過度增生的治療 3 第二節 環孢素(Cyclosporin A, CsA) 3 2-1 Cyclosporin A 的簡介 4 2-2 Cyclosporin A 的作用機轉 4 2-3 Cyclosporin A 與牙齦過度增生 4 第三節 轉化生長因子-β1(TGF-β1) 5 3-1 TGF-β1 的簡介 5 3-2 TGF-β1的訊息傳遞路徑 6 3-3 TGF-β1 與纖維化 7 第四節 離氨基氧化酶樣蛋白-2 (LOXL-2) 9 4-1 LOXL-2 的簡介 9 4-2 LOXL-2 與TGF-β1的訊息傳遞路徑及纖維化 9 研究目的 10 材料與方法 11 第一節 細胞株與細胞培養 11 第二節 藥物處理 11 2-1 Cyclosporin A藥物處理 11 2-2 抑制劑、中和抗體使用資料 11 第三節 西方墨點法 12 3-1 蛋白萃取 12 3-2 膠體配置與電泳分析 12 3-3 蛋白轉漬 12 3-4 抗體反應與顯影呈色 13 第四節 統計與方法 13 結果 14 Cyclosporin A可誘導牙齦上皮細胞OECM-1及CA9-22之LOXL-2的表現 14 Cyclosporin A經由TGF-β訊息傳導路徑誘導OECM-1及CA9-22之LOXL-2表現 14 LOXL-2在Cyclosporin A誘導的EMT扮演重要的角色 14 討論 15 圖與表 17 參考文獻 23 | |
dc.language.iso | zh-TW | |
dc.title | 環孢素在牙齦上皮細胞中經由轉化生長因子β及離氨基氧化酶樣蛋白2 誘導上皮-間質轉換 | zh_TW |
dc.title | Cyclosporin-A induced EMT through TGF-β and LOXL-2 pathways in gingival epithelial cells | en |
dc.type | Thesis | |
dc.date.schoolyear | 107-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 周涵怡,張瑞青 | |
dc.subject.keyword | 環孢素,牙齦過度增生,轉化生長因子-β,上皮-間質細胞轉換,離氨基氧化?樣蛋白2, | zh_TW |
dc.subject.keyword | Cyclosporin A,Gingival overgrowth,TGFβ,EMT,LOXL-2, | en |
dc.relation.page | 32 | |
dc.identifier.doi | 10.6342/NTU201903783 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2019-08-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 臨床牙醫學研究所 | zh_TW |
顯示於系所單位: | 臨床牙醫學研究所 |
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