miR146a在肺成纤维细胞表型转化中的作用和机制

项目名称： miR146a在肺成纤维细胞表型转化中的作用和机制

项目编号： No.81460257

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 石宇红

作者单位： 桂林医学院

项目金额： 48万元

中文摘要： 肺纤维化是严重危害人类健康的疾病，目前机制仍未能明确。资料表明抑制成纤维细胞转化为肌成纤维细胞可达到缓解干燥综合征肺纤维化的目的。NF-κB 及AP-1信号转导是成纤维细胞表型转化的关键，阻断NF-κB 及AP-1信号转导可以影响成纤维细胞表型转化。在前期研究中，我们发现miR146a可影响其靶蛋白TRAF6及PI3K的表达从而调控NF-κB信号转导通路。因此我们提出假设：miR146a可能是影响肺成纤维细胞表型转化的关键信号，上调miR-146a可抑制成纤维细胞的表型转化。为证实这一假说，我们将观察通过RNA干扰技术减少或增强miR146a表达后，体外培养的肺成纤维细胞向肌成纤维细胞的转化率的变化，为进一步探讨干燥综合征肺纤维的发生机制和防治提供理论支持。

中文关键词： 干燥综合征；miR146a；肺间质纤维化；成纤维细胞；表型转化

英文摘要： Pulmonary fibrosis is a serious disease.While the mechanism is still in searching.It has been reported that pulmonary fibrosis of sjogren syndrome could be relieved when transormation of fibrosis is inhibited.And the juncture of the trasormation are the signal transduction of NF-κB and AP-1.When we stop these signal trastuction,the transformation of fibroblast is affected. In the previous study, we found that miR146a is the key gene in NF-κB pathway,it can accuse the pathway by control the expression of its target protein of TRAF6 and PI3K. Therefore, we put forward assumption: miR146a may be the key signal of phenotype transormation of fibrosis,by up-regulation of miR146a we can inhibit of transformation in vivo. To prove this hypothesis, we will culture fibroblast of pulmonary in vito,and observe the change of conversion of the fibroblast transformation when the expression of miR146a has been decreased or increased by RNA interference.It can offer theory support for the mechanism and therapy of pulmonary fibrosis of sjogren syndrome.

英文关键词： Sjogren's syndrome;miR146a;pulmonary fibrosis;fibroblast;phenotype transdifferentiation