报告题目：Role of epithelial abnormalities in idiopathic pulmonary fibrosis (IPF)

报告人：周蓓芸，Assistant Professor of Medicine (Tenure track), Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Southern California, Los Angeles, CA

主持人：石铁流 教授

报告时间：9月10日 10:30

报告地点：闵行生科院534报告厅

 

报告人简介：周蓓芸，1982年毕业于bevictor伟德官网生物系，1988年毕业于中科院上海植物生理研究所获得微生物硕士学位，毕业后留所工作，期间到德国比勒费尔德大学访问一年，1999年加入到南加州大学医学院的“肺，重症监护和睡眠医学科”工作到至今，期间，于2008年获得南加州大学医学院的博士学位，现为该学科的助理教授，她长期从事分子药理学和毒理学的研究。主要领域是：肺泡上皮细胞（AEC），Ⅱ型为Ⅰ型细胞转分化；肺泡上皮细胞的可塑性，上皮 - 间质转化（EMT）和肺损伤，修复和纤维化过程中的上皮 - 间充质之间的交互作用；在AEC表观遗传可塑性中的作用等。orders & Therapy期刊主编，同时为Nature Medicine，Cancer Research等许多国际杂志评审。

 

报告摘要：Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, lethal disorder of unknown etiology. Repeated epithelial injury is hypothesized to play a central role in disease pathogenesis. We have previously shown that pulmonary epithelial-specific blocking of transforming growth factor-β (TGF-β) signaling inhibits fibrosis in a mouse model of fibrosis induced by bleomycin suggesting a key role for epithelial cells in development of lung fibrosis. Although we and others have shown that alveolar epithelial cells undergo epithelial-mesenchymal transition (EMT) in response to TGF-β1 and bleomycin injury in vitro and in vivo, the role of EMT in lung fibrogenesis is still controversial. To further examine the role of epithelial abnormalities in the pathogenesis of pulmonary fibrosis, we examined effects of endoplasmic reticulum (ER) stress on induction of EMT and/or activation/reprogramming of alveolar epithelial cells in vitro. We further generated a mouse model with knockout of the ER chaperone glucose-regulated protein 78 (Grp78) specifically in alveolar epithelial cells. Our results indicate that 1) ER stress due to loss of GRP78 induces fibrosis and 2) epithelial reprogramming due to ER stress creates a vulnerable epithelium that is highly susceptible to further injury (e.g., bleomycin) in vivo.