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Mechanosensing by the α 6-integrin confers an invasive fibroblast phenotype and mediates lung fibrosis

Nature Communications, ISSN: 2041-1723, Vol: 7, Issue: 1, Page: 12564
2016
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Article Description

Matrix stiffening is a prominent feature of pulmonary fibrosis. In this study, we demonstrate that matrix stiffness regulates the ability of fibrotic lung myofibroblasts to invade the basement membrane (BM). We identify α 6-integrin as a mechanosensing integrin subunit that mediates matrix stiffness-regulated myofibroblast invasion. Increasing α 6-expression, specifically the B isoform (α 6 B), couples β 1-integrin to mediate MMP-2-dependent pericellular proteolysis of BM collagen IV, leading to myofibroblast invasion. Human idiopathic pulmonary fibrosis lung myofibroblasts express high levels of α 6-integrin in vitro and in vivo. Genetic ablation of α 6 in collagen-expressing mesenchymal cells or pharmacological blockade of matrix stiffness-regulated α 6-expression protects mice against bleomycin injury-induced experimental lung fibrosis. These findings suggest that α 6-integrin is a matrix stiffness-regulated mechanosensitive molecule which confers an invasive fibroblast phenotype and mediates experimental lung fibrosis. Targeting this mechanosensing α 6 (β 1)-integrin offers a novel anti-fibrotic strategy against lung fibrosis.

Bibliographic Details

Chen, Huaping; Qu, Jing; Huang, Xiangwei; Kurundkar, Ashish; Zhu, Lanyan; Yang, Naiheng; Venado, Aida; Ding, Qiang; Liu, Gang; Antony, Veena B; Thannickal, Victor J; Zhou, Yong

Springer Science and Business Media LLC

Chemistry; Biochemistry, Genetics and Molecular Biology; Physics and Astronomy

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