Pleural mesothelial cell migration into lung parenchyma by calpain contributes to idiopathic pulmonary fibrosis

Li Ling Zhou, Pei Pei Cheng, Xin Liang He, Li Mei Liang, Meng Wang, Yu Zhi Lu, Lin Jie Song, Liang Xiong, Fei Xiang, Fan Yu, Xiaorong Wang, Jian Bao Xin, Peter A. Greer, Yunchao Su, Wan Li Ma, Hong Ye

Research output: Contribution to journalArticlepeer-review

Abstract

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 using Wt1tm1(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 vitro studies 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.

Original languageEnglish (US)
JournalJournal of Cellular Physiology
DOIs
StateAccepted/In press - 2021

Keywords

  • calpain
  • fibrosis
  • migration
  • pleural mesothelial cell

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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