Pleural mesothelial cell migration into lung parenchyma by calpain contributes to idiopathic pulmonary fibrosis
Pleural mesothelial cell migration into lung parenchyma by calpain contributes to idiopathic pulmonary fibrosis
复制标题
钙蛋白酶导致胸膜间皮细胞迁移至肺实质，导致特发性肺纤维化
DOI：
10.1002/jcp.30500
复制
发表时间：
2021-07-06
影响因子：
5.6
通讯作者：
Ye，Hong
中科院分区：
文献类型：
--
作者：
Zhou，Li-Ling;Cheng，Pei-Pei;Ye，Hong
Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia. It is unknown why fibrosis in IPF distributes in the peripheral or named sub‐pleural area. Migration of pleural mesothelial cells (PMC) should contribute to sub‐pleural fibrosis. Calpain is known to be involved in cell migration, but the role of calpain in PMC migration has not been investigated. In this study, we found that PMCs migrated into lung parenchyma in patients with IPF. Then usingWt1tm1(EGFP/Cre)Wtp/J knock‐in mice, we observed PMC migration into lung parenchyma in bleomycin‐induced pleural fibrosis models, and calpain inhibitor attenuated pulmonary fibrosis with prevention of PMC migration.In vitrostudies revealed that bleomycin and transforming growth factor‐β1 increased calpain activity in PMCs, and activated calpain‐mediated focal adhesion (FA) turnover as well as cell migration, cell proliferation, and collagen‐I synthesis. Furthermore, we determined that calpain cleaved FA kinase in both C‐terminal and N‐terminal regions, which mediated FA turnover. Lastly, the data revealed that activated calpain was also involved in phosphorylation of cofilin‐1, and p‐cofilin‐1 induced PMC migration. Taken together, this study provides evidence that calpain mediates PMC migration into lung parenchyma to promote sub‐pleural fibrosis in IPF.
