特发性肺纤维化（IPF）是一种发病机制不明、治疗效果差的疾病。大量基于动物模型的研究结果并不能说明人IPF的本质。我们前期的研究结果表明：IPF及非IPF患者肺泡上皮细胞均存在上皮-间质细胞转化（EMT）和间质-上皮细胞转化（MET）双向调控，但IPF肺泡上皮细胞MET受阻。本项目拟采用体细胞重编程和诱导多能干细胞（iPSC）分化技术， ①制备IPF及非IPF特异性iPSC分化的肺泡上皮细胞；②观察非IPF肺泡上皮EMT-MET双向调控特征和IPF肺泡上皮MET受阻现象；③研究TGF-β信号通路在IPF肺泡上皮MET受阻中的作用；④筛选调控非IPF肺泡上皮MET发生和IPF肺泡上皮MET受阻的“关键信号通路” , 并在原代培养的IPF肺泡上皮细胞中验证此通路。通过本研究可阐明IPF肺泡上皮细胞EMT-MET双向调控及MET受阻的分子机制，为IPF的发病机制提供新的理论，寻找新的治疗靶点。

Idiopathic pulmonary fibrosis (IPF) is a chronic disease with unknown pathogenesis and poor treatment. However, most of the conclusions on IPF are from animal models and could not elucidate the truth of human IPF. In our early research, it was found that there exist EMT-MET (epithelial mesenchymal transition-mesenchymal epithelial transition) bi-directional regulation in alveolar epithelial cells of both IPF patients and non-IPF patients. However there is no MET happened after EMT and removal of the induced factors in alveolar epithelial cells of IPF patients. This conclusion may be an important pathogenesis of IPF. Because it is so difficult to get enough human lung samples, we could not do more deep research on this area. In this research, we will use somatic cell reprogramming and induced pluripotent stem cell (iPSC) technology, ① to prepare alveolar epithelial cells from iPSC of both IPF and non-IPF patients; ② to confirm EMT-MET bi-directional regulation in alveolar epithelial cells of both IPF and non-IPF patients and MET blockade in IPF patients; ③ to observe the effect of TGF-βsignal passway in MET blockade of alveolar epithelial cells in IPF patients; ④ to screen the “key signal pathway” in MET in alveolar epithelial cells of both IPF and non-IPF patients and to confirm the “key signal pathway” in MET in cultured human alveolar epithelial cells derived from both IPF lung samples and non-IPF patients lung samples. Based on this research, we will elucidate the molecular mechanics of EMT-MET bi-directional regulation and MET blockade in alveolar epithelial cells of IPF patients. It will be helpful to clarify the pathogenesis of IPF and provide a new target point of treatment to IPF.