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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳玉怜(Yuh-Lien Chen) | |
| dc.contributor.author | Ling-Yi Hung | en |
| dc.contributor.author | 洪菱憶 | zh_TW |
| dc.date.accessioned | 2021-06-16T22:58:45Z | - |
| dc.date.available | 2015-09-18 | |
| dc.date.copyright | 2012-09-18 | |
| dc.date.issued | 2012 | |
| dc.date.submitted | 2012-08-08 | |
| dc.identifier.citation | Akoz, T., Gideroglu, K., and Akan, M. (2002). Combination of different techniques for the treatment of earlobe keloids. Aesthetic Plast Surg 26, 184-188.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/64763 | - |
| dc.description.abstract | 蟹足腫是異常增生的疤痕組織，具有大量細胞外基質堆積及異常細胞素活性的特徵。許多證據指出，thalidomide (化學名為N-phthalidomidoglutamide) 含有抗血管新生、抗發炎反應、及免疫調節的特性。過去的研究也發現thalidomide具有抗纖維化的療效，能有效減少細胞外基質的堆積。我們將臨床取得的皮膚檢體進行免疫組織染色，發現蟹足腫檢體相較於正常皮膚檢體表現大量的TGF-β1及fibronectin。將正常及蟹足腫檢體所分離出的纖維母細胞進行體外實驗，發現TGF-β1可誘導fibronectin大量表現，在處理thalidomide的組別中發現其能有效的抑制fibronectin產生。而在實驗中也證實了TGF-β1可以活化MAPKs (ERK1/2、p38及JNK) 和SMADs (Smad2及Smad3) 的磷酸化，但在分別先處理PD98059 (ERK抑制劑) 、SB203580 (p38抑制劑) 及SP600125 (JNK抑制劑) 以及Smad3小片段干擾核酸時，發現皆可抑制纖維母細胞表現fibronectin，代表TGF-β1可透過這些訊息傳遞誘導fibronectin的增加。進一步發現thalidomide能有效的抑制p38及Smad3的磷酸化，對於ERK、JNK及Smad2則沒有影響。除此之外，我們也利用電泳遲滯分析法進行細胞核蛋白之AP-1與Smad3/4活性的探討，發現thalidomide可以有效地降低TGF-β1所誘導的AP-1及Smad3/4與DNA結合的活性。利用明膠酶譜法也發現thalidomide可以增加基質金屬蛋白酶MMP9的活性，進而增加fibronectin的降解，以減少fibronectin的表現量。同時我們建立蟹足腫小鼠模式，發現施打thalidomide的小鼠組別確實可以有效的抑制TGF-β1與fibronectin的表現，也減少了蟹足腫纖維母細胞的數量。綜合以上，thalidomide對於蟹足腫疾病具有抗纖維化的療效，可能是透過抑制TGF-β1活化p38及Smad3磷酸化。我們的研究證實了thalidomide對於治療及預防蟹足腫疾病具有極大的潛力。 | zh_TW |
| dc.description.abstract | Keloids are characterized by vigorously continuous production of extracellular matrix protein and aberrant activities of cytokines in the dermis. Growing bodies of evidence indicate that thalidomide, N-phthalidomidoglutamide, has anti-angiogenic, anti-inflammatory, and immunomodulating properties. Thalidomide also possesses the anti-hepato fibrotic effects, due to the reduced TGF-β1 expression. The present study aimed at determining the therapeutic effects of thalidomide on fibronectin expression of transforming growth factor-β (TGF-β)-treated normal and keloid-derived fibroblasts and the underlying mechanism. In surgically removed normal tissue and keloid tissue in human samples, TGF-β1 and fibronectin immunoreactivity was strong in the keloid tissue, but was barely detectable in the normal tissue. TGF-β1 significantly induced fibronectin expression in normal and keloid fibroblasts and the effect was inhibited by pretreatment with thalidomide. TGF-β1 induced MAPKs (ERK1/2, JNK, and p38) and Smad2/3 phosphorylation. Pretreatment with PD98059 (an ERK1/2 inhibitor), SP600125 (a JNK inhibitor), or SB203580 (a p38 inhibitor) inhibited the TGF-β1-induced fibronectin expression. Furthermore, pretreatment with thalidomide effectively inhibited the phosphorylation of p38 and Smad-3, but not JNK , ERK and Smad2 induced by TGF-β1. In addition, thalidomide pretreatment effectively inhibited TGF-β-induced AP-1 and Smad3/4 DNA binding activity by electrophoretic mobility shift assay. Moreover, thalidomide treatment caused fibronectin degradation through increasing the activity of matrix metalloproteinase 9 by gelatin zymography. We also found that treatment with thalidomide significantly suppressed the production of TGF-β1 and fibronectin as well as the cell number in the in vivo keloid model. These results suggested that thalidomide exerted antifibrotic effect on keloid and the effect may be mediated by the suppression of the TGF-β-induced p38 and Smad3 signaling. Our findings indicated that thalidomide may be a potential drug candidate for the treatment and prevention of keloids. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-16T22:58:45Z (GMT). No. of bitstreams: 1 ntu-101-R99446017-1.pdf: 3410125 bytes, checksum: eb30cf86e42d32267365a4d108e81052 (MD5) Previous issue date: 2012 | en |
| dc.description.tableofcontents | 中文摘要 I
Abstract II 壹、 緒論 4 一、 蟹足腫致病機轉與治療方式 4 1. 流行病學 4 2. 病理學機轉 4 3. 傷口癒合與蟹足腫的關係 5 4. 處理及治療方式 6 二、 參與調控蟹足腫病理機轉的分子 8 1. 乙型轉型生長因子 (TGF-β) 8 2. Mitogen-activated protein kinases (MAPK) 10 3. Sma and Mad Related Family (SMAD) 11 4. Fibronectin 12 三、 Thalidomide 的藥理性質應用與作用機轉 12 四、 研究動機 15 貳、 實驗材料 16 一、儀器設備 16 二、實驗材料與試劑 16 1. 細胞培養 (Cell culture) 16 2. 細胞活性分析法 (MTT assay) 17 3. 西方墨點法 (Western blot assay) 17 4. 小片段干擾RNA 18 5. 組織化學染色 (immunohistochemistry) 18 6. 蘇木精－伊紅色法 (Hematoxylin-eosin staining) 18 7. 免疫細胞化學染色 (Immunocytochemistry) 18 8. 核蛋白萃取 19 9. 核酸凝膠遲滯分析法 (Electrophoretic mobility-shift assay) 19 10. 明膠酶譜法 (Gelatin Zymography) 19 11. 動物實驗 20 12. Creatinine/ BUN濃度測量 20 13. 實驗中所加之藥劑 20 三、 實驗用溶液配方 20 參、 實驗方法 23 1. 人類皮膚纖維母細胞初代培養 23 2. 細胞活性分析 (MTT assay) 23 3. 西方墨點法 (Western blot analysis) 23 4. 小片段干擾RNA 26 5. 組織石蠟包埋 27 6. 免疫組織化學法 (Immunohistochemistry) 28 7. 蘇木精-伊紅染色 (Hematoxylin-Eosin stain) 29 8. 免疫細胞化學染色法 (Immunocytochemistry) 30 9. 核蛋白萃取 31 10. 核酸凝膠電泳遲滯分析法 (Electrophoretic mobility-shift assay) 31 11. 明膠酶譜法 (Gelatin Zymography) 33 12. 動物實驗 33 13. Creatinine 濃度測量 34 14. BUN 濃度測量 35 15. 數據統計分析 35 肆、 實驗結果 36 蟹足腫皮膚組織表現較多TGF-β1及fibronectin 36 以100 μg/mL Thalidomide處理對人類纖維母細胞不具毒性 36 TGF-β1刺激人類纖維母細胞表現fibronectin 36 Thalidomide減少TGF-β1誘發人類纖維母細胞fibronectin的產生 37 探討thalidomide對人類纖維母細胞MAPKs訊息傳遞的影響 37 探討thalidomide對人類纖維母細胞SMADs訊息傳遞的影響 39 Thalidomide 抑制MAPKs下游轉錄因子AP-1的活性 40 AP-1參與TGF-β1刺激人類纖維母細胞fibronectin蛋白的轉錄 41 Thalidomide 抑制SMADs下游轉錄因子Smad3/4的活性 41 Thalidomide促進人類纖維母細胞fibronectin的降解 42 Thalidomide抑制小鼠蟹足腫TGF-β1 及fibronectin表現 43 Thalidomide抑制小鼠蟹足腫細胞增生數量 44 伍、 討論與結論 45 陸、 參考文獻 50 柒、 附圖 63 | |
| dc.language.iso | zh-TW | |
| dc.subject | 蟹足腫 | zh_TW |
| dc.subject | fibronectin | zh_TW |
| dc.subject | thalidomide | zh_TW |
| dc.subject | 乙型轉型生長因子 | zh_TW |
| dc.subject | keloid | en |
| dc.subject | TGF-β | en |
| dc.subject | thalidomide | en |
| dc.subject | fibronectin | en |
| dc.title | Thalidomide 減少 TGF-β1誘導之蟹足腫纖維母細胞之Fibronectin的表現 | zh_TW |
| dc.title | Thalidomide Suppresses Transforming Growth Factor-β1-Induced Fibronectin Expression in Keloid Fibroblasts | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 100-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 王淑美(Seu-Mei Wang),江美治(Mei-Chih Chiang),吳建春(Jiahn-Chun Wu),李繼源(Chi-Yuan Li) | |
| dc.subject.keyword | 蟹足腫,乙型轉型生長因子,thalidomide,fibronectin, | zh_TW |
| dc.subject.keyword | keloid,TGF-β,thalidomide,fibronectin, | en |
| dc.relation.page | 82 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2012-08-08 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 解剖學暨生物細胞學研究所 | zh_TW |
| 顯示於系所單位： | 解剖學暨細胞生物學科所 | |
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