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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 郭彥彬 | zh_TW |
| dc.contributor.advisor | Mark Yen-Ping Kuo | en |
| dc.contributor.author | 徐百鍊 | zh_TW |
| dc.contributor.author | Pai-Lien Hsu | en |
| dc.date.accessioned | 2024-08-19T16:44:02Z | - |
| dc.date.available | 2024-08-20 | - |
| dc.date.copyright | 2024-08-19 | - |
| dc.date.issued | 2024 | - |
| dc.date.submitted | 2024-07-30 | - |
| dc.identifier.citation | 1. Lang NP, Berglundh T, Giannobile WV, Sanz M. Lindhe's clinical periodontology and implant dentistry: John Wiley & Sons, 2021.
2. Beaumont J, Chesterman J, Kellett M, Durey K. Gingival overgrowth: Part 1: aetiology and clinical diagnosis. British dental journal 2017;222:85-91. 3. Bökenkamp A, Bohnhorst B, Beier C, Albers N, Offner G, Brodehl J. Nifedipine aggravates cyclosporine A-induced gingival hyperplasia. Pediatric nephrology 1994;8:181-185. 4. Bharti V, Bansal C. Drug-induced gingival overgrowth: The nemesis of gingiva unravelled. Journal of Indian Society of Periodontology 2013;17:182-187. 5. Shimada T, Takemiya T, Sugiura H, Yamagata K. Role of inflammatory mediators in the pathogenesis of epilepsy. Mediators of inflammation 2014;2014. 6. Trackman P, Kantarci A. Molecular and clinical aspects of drug-induced gingival overgrowth. Journal of dental research 2015;94:540-546. 7. Ibrahim M, Abouzaid M, Mehrez M, El Din HG, El Kamah G. Genetic disorders associated with gingival enlargement. Gingival Diseases-Their Aetiology, Prevention and Treatment: IntechOpen, 2011. 8. Luef G, Burtscher J, Kremser C, Birbamer G, Aichner F, Bauer G, Felber S. Magnetic resonance volumetry of the cerebellum in epileptic patients after phenytoin overdosages. European neurology 1996;36:273-277. 9. Barclay C, McLean M, Hagen N, Brownell A, MacRae M. Severe phenytoin hypersensitivity with myopathy: a case report. Neurology 1992;42:2303-2303. 10. Hassell TM, Hefti AF. Drug-induced gingival overgrowth: old problem, new problem. Critical Reviews in Oral Biology & Medicine 1991;2:103-137. 11. Lucas RM, Howell LP, Wall BA. Nifedipine‐induced gingival hyperplasia: A histochemical and ultrastructural study. Journal of periodontology 1985;56:211-215. 12. Seymour R, Thomason J, Ellis J. The pathogenesis of drug‐induced gingival overgrowth. Journal of clinical periodontology 1996;23:165-175. 13. Wynn T. Cellular and molecular mechanisms of fibrosis. The Journal of Pathology: A Journal of the Pathological Society of Great Britain and Ireland 2008;214:199-210. 14. Corrêa JD, Queiroz-Junior CM, Costa JE, Teixeira AL, Silva TA. Phenytoin-induced gingival overgrowth: a review of the molecular, immune, and inflammatory features. International Scholarly Research Notices 2011;2011. 15. Kiwanuka E, Junker JP, Eriksson E. Transforming growth factor β1 regulates the expression of CCN2 in human keratinocytes via Smad‐ERK signalling. International Wound Journal 2017;14:1006-1018. 16. Kantarci A, Cebeci I, Tuncer Ö, Çarin M, Firatli E. Clinical effects of periodontal therapy on the severity of cyclosporin A‐induced gingival hyperplasia. Journal of periodontology 1999;70:587-593. 17. Ilgenli T, Atilla G, Baylas H. Effectiveness of periodontal therapy in patients with drug‐induced gingival overgrowth. Long‐term results. Journal of periodontology 1999;70:967-972. 18. Thariny E. Comparison Of Gingival Overgrowth Status Between Drug Induced And Inflammatory Gingival Overgrowth. NVEO-NATURAL VOLATILES & ESSENTIAL OILS Journal| NVEO 2021:6040-6053. 19. Borel JF, Feurer C, Magnee C, Stähelin H. Effects of the new anti-lymphocytic peptide cyclosporin A in animals. Immunology 1977;32:1017. 20. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. The international journal of biochemistry & cell biology 2007;39:44-84. 21. Borel JF, Feurer C, Gubler H, Stähelin H. Biological effects of cyclosporin A: a new antilymphocytic agent. Agents and actions 1994;43:179-186. 22. Tungare S, Paranjpe AG. Drug induced gingival overgrowth. StatPearls [Internet]: StatPearls Publishing, 2022. 23. Seymour R, Ellis J, Thomason J. Risk factors for drug‐induced gingival overgrowth. Journal of Clinical Periodontology: Review article 2000;27:217-223. 24. Cotrim P, Martelli‐Junior H, Graner E, Sauk JJ, Coletta R. Cyclosporin A induces proliferation in human gingival fibroblasts via induction of transforming growth factor‐β1. Journal of periodontology 2003;74:1625-1633. 25. Sume SS, Kantarci A, Lee A, Hasturk H, Trackman PC. Epithelial to mesenchymal transition in gingival overgrowth. The American journal of pathology 2010;177:208-218. 26. Derynck R, Jarrett JA, Chen EY, Eaton DH, Bell JR, Assoian RK, et al. Human transforming growth factor-β complementary DNA sequence and expression in normal and transformed cells. Nature 1985;316:701-705. 27. Crane JL, Cao X. Bone marrow mesenchymal stem cells and TGF-β signaling in bone remodeling. The Journal of clinical investigation 2014;124:466-472. 28. Annes JP, Munger JS, Rifkin DB. Making sense of latent TGFβ activation. Journal of cell science 2003;116:217-224. 29. Koli K, Myllärniemi M, Keski-Oja J, Kinnula VL. Transforming growth factor-β activation in the lung: focus on fibrosis and reactive oxygen species. Antioxidants & redox signaling 2008;10:333-342. 30. Hayashi H, Sakai T. Biological significance of local TGF-β activation in liver diseases. Frontiers in physiology 2012;3:20856. 31. Kang JS, Liu C, Derynck R. New regulatory mechanisms of TGF-β receptor function. Trends in cell biology 2009;19:385-394. 32. Schmierer B, Hill CS. TGFβ–SMAD signal transduction: molecular specificity and functional flexibility. Nature reviews Molecular cell biology 2007;8:970-982. 33. Rahimi RA, Leof EB. TGF‐β signaling: A tale of two responses. Journal of cellular biochemistry 2007;102:593-608. 34. Vander Ark A, Cao J, Li X. TGF-β receptors: In and beyond TGF-β signaling. Cellular signalling 2018;52:112-120. 35. Dai X, Hua D, Lu X. Roles of TGF-β in cancer hallmarks and emerging onco-therapeutic design. Expert Reviews in Molecular Medicine 2022;24:e42. 36. Zhang M, Zhang YY, Chen Y, Wang J, Wang Q, Lu H. TGF-β signaling and resistance to cancer therapy. Frontiers in cell and developmental biology 2021;9:786728. 37. Chen S-J, Yuan W, Mori Y, Levenson A, Varga J, Trojanowska M. Stimulation of type I collagen transcription in human skin fibroblasts by TGF-β: involvement of Smad 3. Journal of Investigative Dermatology 1999;112:49-57. 38. Bonniaud P, Kolb M, Galt T, Robertson J, Robbins C, Stampfli M, et al. Smad3 null mice develop airspace enlargement and are resistant to TGF-β-mediated pulmonary fibrosis. The Journal of Immunology 2004;173:2099-2108. 39. Kuru L, Yilmaz S, Kuru B, Kose KN, Noyan U. Expression of growth factors in the gingival crevice fluid of patients with phenytoin-induced gingival enlargement. Archives of oral biology 2004;49:945-950. 40. Buduneli N, Kutukculer N, Aksu G, Atilla G. Evaluation of transforming growth factor-beta 1 level in crevicular fluid of cyclosporin A-treated patients. Journal of periodontology 2001;72:526-531. 41. Zeisberg M, Hanai J-i, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R. BMP-7 counteracts TGF-β1–induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nature medicine 2003;9:964-968. 42. Sato M, Muragaki Y, Saika S, Roberts AB, Ooshima A. Targeted disruption of TGF-β1/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction. The Journal of clinical investigation 2003;112:1486-1494. 43. Rygiel KA, Robertson H, Marshall HL, Pekalski M, Zhao L, Booth TA, et al. Epithelial–mesenchymal transition contributes to portal tract fibrogenesis during human chronic liver disease. Laboratory investigation 2008;88:112-123. 44. Willis BC, Liebler JM, Luby-Phelps K, Nicholson AG, Crandall ED, Du Bois RM, Borok Z. Induction of epithelial-mesenchymal transition in alveolar epithelial cells by transforming growth factor-β1: potential role in idiopathic pulmonary fibrosis. The American journal of pathology 2005;166:1321-1332. 45. Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, et al. Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nature medicine 2007;13:952-961. 46. Ribera J, Pauta M, Melgar-Lesmes P, Córdoba B, Bosch A, Calvo M, et al. A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury. American Journal of Physiology-Gastrointestinal and Liver Physiology 2017;313:G492-G504. 47. Hashimoto N, Phan SH, Imaizumi K, Matsuo M, Nakashima H, Kawabe T, et al. Endothelial–mesenchymal transition in bleomycin-induced pulmonary fibrosis. American journal of respiratory cell and molecular biology 2010;43:161-172. 48. Xavier S, Vasko R, Matsumoto K, Zullo JA, Chen R, Maizel J, et al. Curtailing endothelial TGF-β signaling is sufficient to reduce endothelial-mesenchymal transition and fibrosis in CKD. Journal of the American Society of Nephrology 2015;26:817-829. 49. Garg K, Corona BT, Walters TJ. Therapeutic strategies for preventing skeletal muscle fibrosis after injury. Front Pharmacol 2015;6:87. 50. Yamada M, Kuwano K, Maeyama T, Yoshimi M, Hamada N, Fukumoto J, et al. Gene transfer of soluble transforming growth factor type II receptor by in vivo electroporation attenuates lung injury and fibrosis. J Clin Pathol 2007;60:916-920. 51. Fukasawa H, Yamamoto T, Suzuki H, Togawa A, Ohashi N, Fujigaki Y, et al. Treatment with anti-TGF-beta antibody ameliorates chronic progressive nephritis by inhibiting Smad/TGF-beta signaling. Kidney Int 2004;65:63-74. 52. Gagliardini E, Benigni A. Role of anti-TGF-beta antibodies in the treatment of renal injury. Cytokine Growth Factor Rev 2006;17:89-96. 53. Nakamura T, Sakata R, Ueno T, Sata M, Ueno H. Inhibition of transforming growth factor beta prevents progression of liver fibrosis and enhances hepatocyte regeneration in dimethylnitrosamine-treated rats. Hepatology 2000;32:247-255. 54. Breitkopf K, Haas S, Wiercinska E, Singer MV, Dooley S. Anti-TGF-beta strategies for the treatment of chronic liver disease. Alcohol Clin Exp Res 2005;29:121S-131S. 55. Teekakirikul P, Eminaga S, Toka O, Alcalai R, Wang L, Wakimoto H, et al. Cardiac fibrosis in mice with hypertrophic cardiomyopathy is mediated by non-myocyte proliferation and requires Tgf-beta. J Clin Invest 2010;120:3520-3529. 56. Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J 2004;18:816-827. 57. Iturbide A, García de Herreros A, Peiró S. A new role for LOX and LOXL 2 proteins in transcription regulation. The FEBS journal 2015;282:1768-1773. 58. Mayorca-Guiliani A, Erler JT. The potential for targeting extracellular LOX proteins in human malignancy. OncoTargets and therapy 2013:1729-1735. 59. Peinado H, del Carmen Iglesias‐de la Cruz M, Olmeda D, Csiszar K, Fong KS, Vega S, et al. A molecular role for lysyl oxidase‐like 2 enzyme in snail regulation and tumor progression. The EMBO journal 2005;24:3446-3458. 60. Barry-Hamilton V, Spangler R, Marshall D, McCauley S, Rodriguez HM, Oyasu M, et al. Allosteric inhibition of lysyl oxidase–like-2 impedes the development of a pathologic microenvironment. Nature medicine 2010;16:1009-1017. 61. Mareel M, Vleminckx K, Vermeulen S, Bracke M, Van Roy F. E-cadherin expression: a counterbalance for cancer cell invasion. Bulletin du cancer 1992;79:347-355. 62. Wen B, Xu L-Y, Li E-M. LOXL2 in cancer: regulation, downstream effectors and novel roles. Biochimica et Biophysica Acta (BBA)-Reviews on Cancer 2020;1874:188435. 63. Gilkes DM, Semenza GL, Wirtz D. Hypoxia and the extracellular matrix: drivers of tumour metastasis. Nature Reviews Cancer 2014;14:430-439. 64. Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer cell 2012;21:309-322. 65. Kalluri R, Zeisberg M. Fibroblasts in cancer. Nature reviews cancer 2006;6:392-401. 66. Mueller MM, Fusenig NE. Friends or foes—bipolar effects of the tumour stroma in cancer. Nature Reviews Cancer 2004;4:839-849. 67. Öhlund D, Elyada E, Tuveson D. Fibroblast heterogeneity in the cancer wound. Journal of Experimental Medicine 2014;211:1503-1523. 68. Nazemi M, Rainero E. Cross-talk between the tumor microenvironment, extracellular matrix, and cell metabolism in cancer. Frontiers in oncology 2020;10:239. 69. Ezzoukhry Z, Henriet E, Piquet L, Boyé K, Bioulac-Sage P, Balabaud C, et al. TGF-β1 promotes linear invadosome formation in hepatocellular carcinoma cells, through DDR1 up-regulation and collagen I cross-linking. European journal of cell biology 2016;95:503-512. 70. Liu X, Liu T, Hu L, Jiang T, Liu H, Wang Y, et al. Identification and characterization of the promoter of cancer-related gene LOXL2. Experimental Cell Research 2020;387:111786. 71. Peng T, Lin S, Meng Y, Gao P, Wu P, Zhi W, et al. LOXL2 small molecule inhibitor restrains malignant transformation of cervical cancer cells by repressing LOXL2-induced epithelial-mesenchymal transition (EMT). Cell Cycle 2022;21:1827-1841. 72. Lu YJ, Deng YT, Ko HH, Peng HH, Lee HC, Kuo MYP, Cheng SJ. Lysyl oxidase‐like 2 promotes stemness and enhances antitumor effects of gefitinib in head and neck cancer via IFIT1 and IFIT3. Cancer Science 2023;114:3957-3971. 73. D'Autréaux B, Toledano MB. ROS as signalling molecules: mechanisms that generate specificity in ROS homeostasis. Nature reviews Molecular cell biology 2007;8:813-824. 74. Murdoch CE, Zhang M, Cave AC, Shah AM. NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure. Cardiovascular research 2006;71:208-215. 75. Lampe V, Milobedzka J. Studien über curcumin. Berichte d. D. Chem Gesellschaft 1913;46:2235-2240. 76. Mansouri K, Rasoulpoor S, Daneshkhah A, Abolfathi S, Salari N, Mohammadi M, et al. Clinical effects of curcumin in enhancing cancer therapy: A systematic review. BMC cancer 2020;20:1-11. 77. Zheng D, Huang C, Huang H, Zhao Y, Khan MRU, Zhao H, Huang L. Antibacterial mechanism of curcumin: a review. Chemistry & Biodiversity 2020;17:e2000171. 78. Jakubczyk K, Drużga A, Katarzyna J, Skonieczna-Żydecka K. Antioxidant potential of curcumin—A meta-analysis of randomized clinical trials. Antioxidants 2020;9:1092. 79. Sun X, Liu Y, Li C, Wang X, Zhu R, Liu C, et al. Recent advances of curcumin in the prevention and treatment of renal fibrosis. BioMed research international 2017;2017. 80. Liu D, Gong L. Curcumin inhibits transforming growth factor β induced differentiation of mouse lung fibroblasts to myofibroblasts. Frontiers in pharmacology 2016;7:215092. 81. Chang JZC, Yang WH, Deng YT, Chen HM, Kuo MYP. Thrombin‐stimulated connective tissue growth factor (CTGF/CCN2) production in human buccal mucosal fibroblasts: Inhibition by epigallocatechin‐3‐gallate. Head & Neck 2012;34:1089-1094. 82. Yang W-H, Kuo M-P, Liu C-M, Deng Y-T, Chang H-H, Chang J-C. Curcumin inhibits TGFβ1-induced CCN2 via Src, JNK, and Smad3 in gingiva. Journal of Dental Research 2013;92:629-634. 83. Chen YW, Yang WH, Wong MY, Chang HH, Yen‐Ping Kuo M. Curcumin inhibits thrombin‐stimulated connective tissue growth factor (CTGF/CCN2) production through c‐Jun NH2‐terminal kinase suppression in human gingival fibroblasts. Journal of periodontology 2012;83:1546-1553. 84. Cicha I, Goppelt‐Struebe M. Connective tissue growth factor: context‐dependent functions and mechanisms of regulation. Biofactors 2009;35:200-208. 85. Yang W, Deng Y, Hsieh Y, Wu K, Kuo M. NADPH oxidase 4 mediates TGFβ1-induced CCN2 in gingival fibroblasts. Journal of dental research 2015;94:976-982. 86. Leu T-H, Su SL, Chuang Y-C, Maa M-C. Direct inhibitory effect of curcumin on Src and focal adhesion kinase activity. Biochemical pharmacology 2003;66:2323-2331. | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94808 | - |
| dc.description.abstract | 環孢素A（Cyclosporin A）為一種免疫抑制劑，常用於器官移植的患者，服用此藥物的患者大約有七成會出現副作用牙齦過度增生（Gingival overgrowth，GO），進而導致患者美觀、功能以及生活上受影響。近期研究發現GO的組織中在結締組織及上皮有大量表現的離氨基氧化酶樣蛋白2（Lysyl Oxidase-like protein 2, LOXL2），且LOXL2也因為可以造成上皮間質轉化（Epithelial-mesenchymal transition, EMT）而被認為可能是器官纖維化的治療標的。先前實驗室以抑制劑研究，發現環孢素在人類牙齦上皮細胞Ca9-22中可能經由TGF-β1及LOXL2誘導EMT的產生。本研究確認以TGF-β1處理人類牙齦上皮細胞Ca9-22及另一株牙齦上皮細胞OECM-1可誘導LOXL2的表現。表皮生長因子（EGFR）抑制劑AG1478、NF-kB抑制劑BAY 11-7082、PI3K抑制劑LY294002能夠明顯降低TGF-β1誘導Ca9-22細胞中LOXL2的表現。顯示TGF-β非典型路徑可經由EGFR、NF-kB 、PI3K 訊息傳導路徑誘導LOXL2的表現。LOXL2 siRNA能明顯降低TGF-β1誘導Ca9-22的EMT標誌蛋白N-Cadherin、Vimentin、Snail表現，確認LOXL2在TGF-β誘導Ca9-22的EMT扮演重要的角色。活性氧化物（Reactive oxygen species, ROS）可以調節Cyclosporin A誘導牙齦上皮細胞Ca9-22及OECM-1中LOXL2的表現。薑黃素（Curcumin）可以降低Cyclosporin A與TGF-β1誘導牙齦上皮細胞Ca9-22及另一株牙齦上皮細胞OECM-1的LOXL2表現。當Curcumin濃度到達2.5μM時，即開始顯著抑制Ca9-22及OECM-1細胞中LOXL2表現，並具有劑量依賴效應。從這些結果中我們確認Cyclosporin A在口腔上皮細胞中可以經由TGF-β1誘導LOXL2促使EMT的產生。薑黃素可以經由抑制TGF-β1誘導LOXL2的表現，進而阻斷LOXL2所帶來對於口腔上皮細胞的EMT現象，而成為具有防治GO潛力的藥物。 | zh_TW |
| dc.description.abstract | Background: Cyclosporin A is an immunosuppressant commonly used in organ transplant patients. Approximately 70% of patients taking this medication experience side effects gingival overgrowth, which may impair their esthetic, function, and quality of life. Current research indicates that, Lysyl Oxidase-like protein 2 (LOXL2) is associated with epithelial-mesenchymal transition (EMT), leading to tissue overgrowth. Previous studies from our laboratory using chemical inhibitors have shown that Cyclosporin A led to EMT possibly through TGF-β and LOXL2 in gingival epithelium cell. The aim of this study is to find out the correlation between Cyclosporin A, TGF-β and LOXL2 during EMT in human gingival cells.
Materials and methods: Two human gingival cell lines (Ca9-22 and OECM-1) were used in this study. The levels of LOXL2 and EMT associated markers, N-cadherin, vimentin and Snail were analyzed by Western blot. Result: TGF-β1 increased LOXL2 expression in Ca9-22 and OECM-1 cells in the dose of 2ng/ml and time-dependent manner. Pretreatment with EGFR inhibitor AG1478, NF-kB inhibitor BAY 11-7082(BAY) and PI3K inhibitor LY294002 suppressed TGF-β1-induced LOXL2 synthesis in Ca9-22. This indicate that LOXL2 expression is induced from TGF-β1 through EGFR, NF-kB and PI3K in noncanonical pathway. Reactive oxygen species (ROS) such as xanthine oxidase, NOX2, NOX4, NOS and mitochondrial ROS can regulate the expression of Cyclosporin A-induced LOXL2 expression in human gingival cells. Furthermore, curcumin decreased Cyclosporin A- and TGF-β1-induced LOXL2 expression in Ca9-22 and OECM-1 cells in a dose dependent manner. At concentration of 2.5μM, curcumin significantly inhibited LOXL2 expression in human gingival epithelial cells. Conclusions: TGF-β1 increased LOXL2 expression through EGFR, NF-kB and PI-3K signaling in human gingival epithelial cells. LOXL2 is required for TGF-β1-induced EMT in human gingival epithelial cells. Curcumin decreased Cyclosporin A- and TGF-β1-induced LOXL2 expression at a concentration of 2.5μM in human gingival epithelial cells. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2024-08-19T16:44:02Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2024-08-19T16:44:02Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 目次
口試委員會審定書 I 誌謝 II 中文摘要 III Abstract IV 目次 V 導論 1 第一章 牙齦過度增生(Gingival overgrowth) 1 1-1牙齦過度增生(Gingival overgrowth)介紹 1 一、由於發炎引起的局部性牙齦增生(Isolated reactive lesions of the gingiva)： 1 二、一般性牙齦增生 (Generalized gingival enlargement)： 1 1-2 藥物引發牙齦增生的流行病學 3 1-3牙齦過度增生的可能致病機轉 3 1-4牙齦過度增生的治療 4 第二章 環孢素(Cyclosporin A, CsA) 4 2-1 Cyclosporin A的簡介 4 2-2 Cyclosporin A的作用機轉 5 2-3 Cyclosporin A造成牙齦過度增生的機轉 5 第三章 乙型轉型生長因子 (Transforming growth factor-β，TGF-β) 6 3-1 TGF-β 的簡介 6 3-2 TGF-β的訊息傳遞路徑 7 3-3 TGF-β與纖維化 7 第四章 離氨基氧化酶樣蛋白2 (Lysyl Oxidase-like protein 2, LOXL2) 8 4-1 LOX家族簡介 8 4-2 LOXL2之結構與功能 9 4-3 LOXL2之上游調控 9 4-4 LOXL2促進EMT之機轉 10 第五章 活性氧化物 （Reactive oxygen species，ROS） 11 5-1 ROS的簡介 11 5-2 ROS與纖維化 12 第六章 薑黃素（Curcumin） 13 研究目的 14 材料與方法 15 第一章 細胞株與細胞培養 15 第二章 藥物處理 15 2-1 Cyclosporin A以及其他藥物的處理 15 2-2 抑制劑、抗氧化劑使用資料 16 2-3 Cyclosporin A、TGF-β的使用資料 17 第三章 西方墨點法 17 3-1 蛋白萃取 17 3-2 膠體配置與電泳分析 17 3-3 蛋白轉漬 18 3-4 抗體反應與顯影呈色 18 第四章 統計方法 19 結果 20 討論 23 圖與表 25 圖一 ROS抑制劑L-NAME、DPI、Mito-TEMPO、Allopurinol、NAC、Apocynin、Plumbagin會抑制牙齦上皮細胞Ca9-22中Cyclosporin A誘導的LOXL2表現 25 圖二 ROS抑制劑L-NAME、DPI、Mito-TEMPO、Allopurinol、NAC、Apocynin、Plumbagin會抑制牙齦上皮細胞OECM-1中Cyclosporin A誘導的LOXL2表現 26 圖三 TGF-β會誘導牙齦上皮細胞Ca9-22中LOXL2表現 27 圖四 TGF-β會誘導牙齦上皮細胞OECM-1中LOXL2表現 28 圖五 TGF-β會經由EGFR、NF-kB、PI3K誘導牙齦上皮細胞Ca9-22中的LOXL2表現 29 圖六 TGF-β經由LOXL2誘導牙齦上皮細胞Ca9-22產生EMT 30 圖七 Curcumin可抑制牙齦上皮細胞Ca9-22中Cyclosporin A誘導LOXL2之表現 31 圖八 Curcumin可抑制牙齦上皮細胞OECM-1中Cyclosporin A誘導之LOXL2表現 32 圖九 Curcumin可抑制牙齦上皮細胞Ca9-22中TGF-β誘導LOXL2之表現 33 圖十 Curcumin可抑制牙齦上皮細胞OECM-1中TGF-β誘導LOXL2之表現 34 參考文獻 35 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 環孢素A (Cyclosporin A) | zh_TW |
| dc.subject | 牙齦過度增生 (Gingival overgrowth) | zh_TW |
| dc.subject | 離氨基氧化酶樣蛋白2 (Lysyl Oxidase-like protein 2 | zh_TW |
| dc.subject | LOXL2) | zh_TW |
| dc.subject | 轉化生長因子-β (Transforming Growth Factor-β | zh_TW |
| dc.subject | TGF-β) | zh_TW |
| dc.subject | 上皮-間質細胞轉換 (Epithelial-mesenchymal Transition | zh_TW |
| dc.subject | EMT) | zh_TW |
| dc.subject | Lysyl Oxidase-like protein 2 | en |
| dc.subject | Epithelial–mesenchymal transition | en |
| dc.subject | TGF-β | en |
| dc.subject | Transforming Growth Factor-β | en |
| dc.subject | LOXL2 | en |
| dc.subject | Gingival overgrowth | en |
| dc.subject | Cyclosporin A | en |
| dc.title | 薑黃素可抑制環孢素經由TGF-β誘導牙齦上皮細胞的LOXL2表現 | zh_TW |
| dc.title | Curcumin inhibits Cyclosporin A Induced LOXL2 Expression in Gingival Epithelial Cells through TGF-β | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 112-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 張瑞青;呂炫堃 | zh_TW |
| dc.contributor.oralexamcommittee | Jenny Zwei-Chieng Chang;Hsein-Kun Lu | en |
| dc.subject.keyword | 環孢素A (Cyclosporin A),牙齦過度增生 (Gingival overgrowth),離氨基氧化酶樣蛋白2 (Lysyl Oxidase-like protein 2, LOXL2),轉化生長因子-β (Transforming Growth Factor-β, TGF-β),上皮-間質細胞轉換 (Epithelial-mesenchymal Transition, EMT), | zh_TW |
| dc.subject.keyword | Cyclosporin A,Gingival overgrowth,Lysyl Oxidase-like protein 2, LOXL2,Transforming Growth Factor-β, TGF-β,Epithelial–mesenchymal transition, | en |
| dc.relation.page | 43 | - |
| dc.identifier.doi | 10.6342/NTU202402300 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2024-07-30 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 臨床牙醫學研究所 | - |
| Appears in Collections: | 臨床牙醫學研究所 | |
Files in This Item:
| File | Size | Format | |
|---|---|---|---|
| ntu-112-2.pdf Restricted Access | 11.81 MB | Adobe PDF |
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