小柯机器人

北京生命科学研究所汤楠课题组与南京医科大学附属无锡市人民医院陈静瑜教授合作发现，进展性肺纤维化是由肺泡干细胞的机械张力升高引起的。2019年12月19日，国际知名学术期刊《细胞》在线发表了这一成果。

研究人员发现肺泡干细胞（AT2细胞）中Cdc42功能的丧失会导致周围到中心的进行性肺纤维化。研究人员进一步表明，在肺切除术后和未治疗的老年小鼠中，Cdc42缺失的AT2细胞不能再生新的肺泡，从而导致AT2细胞持续暴露于升高的机械张力。研究人员证明升高的机械张力会激活AT2细胞中的TGF-β信号通路，从而驱动肺纤维化的外周向中心发展。这项研究在受损的肺泡再生、机械张力和进行性肺纤维化之间建立了直接的机制联系。

据介绍，纤维化可以在大多数器官中发展并引起器官衰竭。肺纤维化最常见的类型称为特发性肺纤维化，其中纤维化始于肺周围，然后发展至肺中心，最终导致呼吸衰竭。关于该疾病的发病机理和外周至中心进展的机制知之甚少。

附：英文原文

Title: Progressive Pulmonary Fibrosis Is Caused by Elevated Mechanical Tension on Alveolar Stem Cells

Author: Huijuan Wu, Yuanyuan Yu, Huanwei Huang, Yucheng Hu, Siling Fu, Zheng Wang, Mengting Shi, Xi Zhao, Jie Yuan, Jiao Li, Xueyi Yang, Ennan Bin, Dong Wei, Hongbin Zhang, Jin Zhang, Chun Yang, Tao Cai, Huaping Dai, Jingyu Chen, Nan Tang

Issue&Volume: December 19, 2019

Abstract: Fibrosis can develop in most organs and causes organ failure. The most common typeof lung fibrosis is known as idiopathic pulmonary fibrosis, in which fibrosis startsat the lung periphery and then progresses toward the lung center, eventually causingrespiratory failure. Little is known about the mechanisms underlying the pathogenesisand periphery-to-center progression of the disease. Here we discovered that loss ofCdc42 function in alveolar stem cells (AT2 cells) causes periphery-to-center progressivelung fibrosis. We further show that Cdc42-null AT2 cells in both post-pneumonectomy and untreated aged mice cannot regeneratenew alveoli, resulting in sustained exposure of AT2 cells to elevated mechanical tension.We demonstrate that elevated mechanical tension activates a TGF-β signaling loop inAT2 cells, which drives the periphery-to-center progression of lung fibrosis. Ourstudy establishes a direct mechanistic link between impaired alveolar regeneration,mechanical tension, and progressive lung fibrosis.

DOI: 10.1016/j.cell.2019.11.027

Source: https://www.cell.com/cell/fulltext/S0092-8674(19)31284-X