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標題: | 生醫材料對於抑制下呼吸道表皮細胞以及上呼吸道間質細胞之纖維化 The Effects of Biomaterials on Inhibiting Fibrosis of Lung Epithelial Cells and Nasal Fibroblasts |
作者: | Jun-Wei Liu 劉峻瑋 |
指導教授: | 楊台鴻 |
共同指導教授: | 黃琮瑋 |
關鍵字: | 玻尿酸,肺上皮細胞,上皮細胞間質轉化,纖維母細胞,肌纖維母細胞分化, hyaluronan/hyaluronic acid,lung epithelial cell,epithelial-mesenchymal transition,fibroblast,myofibroblast differentiation, |
出版年 : | 2019 |
學位: | 碩士 |
摘要: | 肺纖維化還是現今醫學難以解決的問題,其中以特發性纖維化最為代表,在先前的研究中,我們發現玻尿酸對於上呼吸道的上皮細胞,能透過抑制乙型轉化生長因子的訊號,來抑制上皮細胞間質轉化的功能,進而減緩纖維化。在本篇研究中,我們希望能夠複製玻尿酸在上呼吸道之特性到下呼吸道的上皮細胞,進而達到能抑制肺纖維化的作用。我們利用A549和Nuli-1這兩株細胞來做測試,但根據實驗結果顯示,玻尿酸在A549肺癌細胞上反而會助長上皮細胞間質轉化,而在Nuli-1玻尿酸能讓上皮細胞表現更好的上皮極性,但也無法抑制上皮細胞間質轉化。
另外一方面,纖維母細胞分化成肌纖維母細胞也是造成纖維化的一個原因,本研究我們同樣使用玻尿酸來測試鼻部纖維母細胞分化的情形。根據研究結果,我們發現玻尿酸無法阻止纖維母細胞分化成肌纖維母細胞,甚至單純加入玻尿酸會助長纖維母細胞的爬行速度,但我們發現玻尿酸可以抑制肌纖維母細胞所造成的過量細胞外基質。因此,本研究之結果,我們可以得知上下呼吸道上皮細胞對於玻尿酸的反應是不同的,以及玻尿酸能夠抑制過量細胞外基質產生。 Inhibiting lung fibrosis is still an unmet need, and idiopathic lung fibrosis (IPF) is typical lung fibrosis. In previous reports, we knew that hyaluronan (HA) could antagonize the differentiation effect of TGF-ß1 on nasal epithelial cells through the downregulation of TGF-ß type I receptor. Therefore, in this study, we hope to replicate the effect of HA on upper respiratory epithelial cells to lower respiratory epithelial cells and attenuate lung fibrosis. However, we can’t have the same effect on A549, lung cancer epithelial cells; HA even enhances the epithelial-mesenchymal transition (EMT) on A549. Hyaluronan can evaluate the epithelial integrity but can not reduce the EMT on Nuli-1 either. On the other hand, the differentiation of fibroblasts to myofibroblasts is another reason for fibrosis. In this study, we have observed that HA can not attenuate the myofibroblast differentiation, even the group with HA alone enhance the migration rate of nasal fibroblasts. However, we have found that HA can inhibit the excessive secretion of NFBs, which makes fibrosis worse. Consequently, we have found the effect of HA on upper respiratory and lower respiratory epithelial cells are different. Moreover, HA can inhibit the excessive secretion of myofibroblast through inhibiting TGF-b1 pathway. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/72526 |
DOI: | 10.6342/NTU201902304 |
全文授權: | 有償授權 |
顯示於系所單位: | 醫學工程學研究所 |
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