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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳信銘(Hsin-Ming Chen) | |
dc.contributor.author | Hsiang-He Wang | en |
dc.contributor.author | 王祥合 | zh_TW |
dc.date.accessioned | 2021-06-17T02:11:38Z | - |
dc.date.available | 2020-09-01 | |
dc.date.copyright | 2020-09-01 | |
dc.date.issued | 2020 | |
dc.date.submitted | 2020-08-18 | |
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/68039 | - |
dc.description.abstract | 口腔黏膜下纖維化症(oral submucous fibrosis;OSF)是一種慢性的發炎疾病,特徵在於膠原蛋白過量累積或分解速度下降,導致口腔黏膜的透明硬化。OSF患者的臨床症狀為口腔黏膜灼熱及張口困難。嚼食檳榔被認為是主要的致病因子。嚼食過程檳榔不斷的與口腔黏膜摩擦,引起發炎症狀並產生細胞激素及生長因子,使纖維母細胞分化為肌纖維母細胞(myofibroblasts),導致膠原蛋白的過度增加。目前研究中,尚無OSF可逆性的治療方式。近年來,在肝其其他器官纖維化的研究中發現,維生素D可以透過抑制TGF-β訊息傳遞路徑的Smad 2/3蛋白和α-smooth muscle actin(α-SMA)基因表現,抑制纖維化蛋白表現。因此, 我們從健康受試者與OSF患者口腔黏膜取得的纖維母細胞,進行一系列口腔黏膜細胞纖維化致病機轉的探究。首先,我們檢測了維生素D對OSF纖維母細胞的作用,該作用抑制了pro-collagen 1A1和α-SMA的表達。其次,使用正常口腔黏膜纖維母細胞經TGF-β誘導處理,模擬OSF致病機轉中纖維化的變化。在維生素D作用之後,結果發現維生素D可以有效抑制TGF-β誘導之Smad訊息傳遞路徑中之Smad3蛋白。同時,我們發現維生素D可以抑制p38和JNK的表現(但不能抑制ERK表現),且明顯抑制Pro-collagen1A1及α-SMA的表現。最後,我們在OSF之纖維母細胞中也發現,維生素D亦可透過抑制TGF-β誘導的Smad和Non-Smad路徑中之訊息傳遞蛋白,Smad3、p38 及JNK,抑制纖維化蛋白Pro-collagen1A1及α-SMA的表現。總而言之,不論正常口腔黏膜纖維母細胞經TGF-β誘導所產生之纖維化蛋白表現,或是OSF纖維母細胞纖維化蛋白的表現,都可以被維生素D抑制。因此,維生素D可以預防和緩解OSF的進程。 | zh_TW |
dc.description.abstract | Oral subucous fibrosis (OSF) is a chronic inflammatory oral disease characterized by the overproduction of collagen or reduced collagen degradation, which results in the hyalinization of the oral mucosa. Patients with OSF present burning sensation and difficulty in mouth opening. Betel quid chewing is often recognized as the causative factor for this disease that induces inflammation from micro-abrasions, which generated cytokine and growth factors by the constant friction of the course fibers of the areca nut to the oral mucosa. Meanwhile, fibroblasts were activated to be myofiborblasts, which is highly produce over expression of collagen. Up to now, there is no treatment strategy to reverse OSF to be normal. However, recent studies showed that vitamin D could inhibit the TGF-β-mediated fibrosis development through the suppression of Smad2/3 proteins and α-SMA gene expression. This mechanism consequently resulted in decrease pro-collagen expression. Therefore, vitamin D may provide a promising new treatment modality for reversing OSF. In this study, we obtained primary cultures of fibroblasts from healthy volunteers and OSF patients. First, we detected the effect vitamin D on OSF fibroblasts, which suppressed the expression of pro-collagen 1A1 and α-smooth muscle actin (α-SMA). Then, we used normal oral mucosa fibroblasts (OMF) to be treated by TGF-β cytokine induction on the normal fibroblast to simulately induce the fibrotic change as mimicking the pathogenesis of OSF. Upon exposure to vitamin D, we observed that it was able to block the TGF-β-mediated classic Smad and non-Smad signaling pathway through inhibition of the Smad3, p38 and JNK protein, but not ERK protein, which eventually decreased pro-collagen 1A1 and α-SMA production. Finally, we also found that there was similar suppression of Smad3, p38 and JNK expression in OSF fibroblasts treated by vitamin D. In conclusion, no matter how the fibrogenesis of OMF induced by TGF-β or OSF fibroblasts could be suppressed by vitamin D. Therefore, vitamin D is possibly able to prevent and alleviate OSF progression. | en |
dc.description.provenance | Made available in DSpace on 2021-06-17T02:11:38Z (GMT). No. of bitstreams: 1 U0001-1708202017181700.pdf: 3035402 bytes, checksum: d3c075e201d8925f623b62ecd4b05ead (MD5) Previous issue date: 2020 | en |
dc.description.tableofcontents | 論文口試委員審定書 i 誌謝 ii 中文摘要 iii Abstract iv 目錄 vi 第一章 導論 1 第一節 口腔黏膜下纖維化症(Oral submucous fibrosis;OSF) 1 1-1 口腔黏膜下纖維化症簡介 1 1-2 口腔黏膜下纖維化症的流行病學 1 1-3 纖維化細胞來源 1 1-4 口腔黏膜下纖維化症的發病成因 3 1-5 口腔黏膜下纖維化症與口腔癌 3 1-6 口腔黏膜下纖維化症的治療 4 第二節 轉化生長因子(Transforming growth factor-β;TGF-β) 5 2-1 TGF-β簡介 5 2-2 TGF-β的訊號傳遞路徑 5 2-3 TGF-β與纖維化 7 2-4 TGF-β與EMT 8 3-1 維生素D簡介 9 3-2 維生素D與纖維化 9 3-3 維生素D抑制訊號傳遞路徑 10 3-4 維生素與纖維化過去研究 11 第二章 實驗目的 13 第三章 材料與方法 14 第一節 細胞株與細胞培養 14 1-1 纖維母細胞株的培養 14 1-2 口腔黏膜上皮細胞株培養 14 1-3 繼代培養 14 第二節 藥物處理 15 2-1 細胞培養與Starvation 15 2-2 Vitamin D與TGF-β的處理 15 第三節 西方墨點法(Western blot) 16 3-1蛋白質萃取 16 3-2蛋白質分析 16 3-3膠體配置 16 3-4電泳分析 17 3-5蛋白質轉漬 17 3-6抗體的使用 17 3-7顯影呈色 18 第四節 細胞活性測試(MTT Assay) 19 第五節 Collagen Gel Contraction Assay 20 第六節 siRNA Transfection 21 第四章 結果 22 4-1 Vitamin D對OSF細胞具有抑制效果 22 4-2 TGF-β誘導纖維母細胞(OMF)活化建立纖維化模型 23 4-3 利用膠原蛋白凝膠收縮測定法評估膠原蛋白表現 24 4-4 TGF-β誘導OMF細胞活化Smad3磷酸化表現 25 4-5 Vitamin D可以抑制TGF-β誘導的Smad3磷酸化表現 26 4-6 Vitamin D可以抑制TGF-β的誘導Smad路徑,並阻斷α-SMA表現 27 4-7 Vitamin D可以抑制TGF-β誘導的Non-Smad JNK磷酸化表現 28 4-8 Vitamin D與siRNA皆可以抑制TGF-β誘導的Non-Smad JNK磷酸化表現 29 4-9 Vitamin D可以抑制由TGF-β的誘導Non-Smad路徑上的蛋白,並阻斷α-SMA與Pro-Collagen 1A1蛋白表現 30 4-10 Vitamin D可以抑制OSF細胞纖維化路徑中,p-JNK與p-ERK的磷酸化蛋白表現 31 4-11 Vitamin D可以抑制OSF細胞纖維化路徑中,α-SMA與Pro-Collagen 1A1的蛋白表現 32 第五章 討論 33 第六章 圖與表 36 圖一、Vitamin D對OSF細胞的毒性測試 36 圖二、Vitamin D可以抑制OSF纖維母細胞在纖維化蛋白的表現 37 圖三、Vitamin D對OMF細胞的毒性測試 38 圖四、TGF-β誘導正常OMF細胞活化 39 圖五、Vitamin D可以抑制在Pro-collagen蛋白的表現 40 圖六、Vitamin D對膠原蛋白凝膠的收縮測試 41 圖七、不同濃度與時間的TGF-β誘導纖維母細胞在Smad3的表現 42 圖八、Vitamin D可以抑制TGF-β誘導的Smad3蛋白表現 43 圖九、證實Vitamin D可以抑制OMF細胞TGF-β誘導的Smad路徑 44 圖十、TGF-β誘導Non-smad路徑中的JNK蛋白表現 45 圖十一、證實Vitamin D可以抑制TGF-β誘導的Non-Smad路徑 46 圖十二、Vitamin D的抑制與TGF-β誘導的Non-Smad路徑有正相關 47 圖十三、Vitamin D可經由TGF-β誘導的Non-Smad路徑抑制纖維化相關蛋白 48 圖十四、Vitamin D可以抑制OSF細胞Non-Smad pathway中的磷酸化表現 49 圖十五、Vitamin D可以抑制OSF細胞的纖維化表現透過Smad pathway 50 圖十六、Vitamin D可以抑制OSF細胞的纖維化表現透過Non-Smad pathway 51 圖十七、Vitamin D可以抑制纖維化表現 52 第七章 參考資料 53 | |
dc.language.iso | zh-TW | |
dc.title | 維生素D藉由抑制乙型轉化生長因子多方面訊息傳遞以減弱口腔肌纖維母細胞所致纖維化之研究 | zh_TW |
dc.title | Vitamin D Inhibits Multifaceted Signal Transduction of Tumor Growth Factor-β to Attenuate Fibrogenesis of Oral Myofibroblasts | en |
dc.type | Thesis | |
dc.date.schoolyear | 108-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 江俊斌(Chun-Pin Chiang),周涵怡(Han-Yi Chou),黎萬君(Wan-Chun Li) | |
dc.subject.keyword | 甲型-平滑肌肌動蛋白,膠原蛋白,肌纖維母細胞,口腔黏膜下纖維化症,乙型轉化生長因子,維生素D, | zh_TW |
dc.subject.keyword | alpha-smooth muscle actin,collagen,myofibroblast,oral submucous fibrosis,transforming growth factor-beta,vitamin D, | en |
dc.relation.page | 60 | |
dc.identifier.doi | 10.6342/NTU202003817 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2020-08-18 | |
dc.contributor.author-college | 醫學院 | zh_TW |
dc.contributor.author-dept | 口腔生物科學研究所 | zh_TW |
顯示於系所單位: | 口腔生物科學研究所 |
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U0001-1708202017181700.pdf 目前未授權公開取用 | 2.96 MB | Adobe PDF |
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