Pleural mesothelial cell migration into lung parenchyma by calpain contributes to idiopathic pulmonary fibrosis
Autor: | Yunchao Su, Fan Yu, Jian Bao Xin, Li Mei Liang, Hong Ye, Pei Pei Cheng, Lin Jie Song, Xin Liang He, Yu Zhi Lu, Meng Wang, Xiaorong Wang, Peter A. Greer, Liang Xiong, Wan-Li Ma, Li Ling Zhou, Fei Xiang |
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Rok vydání: | 2021 |
Předmět: |
Pathology
medicine.medical_specialty Physiology Clinical Biochemistry Bleomycin Transforming Growth Factor beta1 Focal adhesion Mice chemistry.chemical_compound Idiopathic pulmonary fibrosis Cell Movement Fibrosis Pulmonary fibrosis Parenchyma medicine Animals Humans Lung biology Calpain business.industry Cell migration Cell Biology respiratory system medicine.disease Idiopathic Pulmonary Fibrosis respiratory tract diseases Actin Depolymerizing Factors chemistry biology.protein business |
Zdroj: | Journal of Cellular Physiology. 237:566-579 |
ISSN: | 1097-4652 0021-9541 |
Popis: | 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. |
Databáze: | OpenAIRE |
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