Soluble E‐cadherin participates in BLM‐induced pulmonary fibrosis by promoting EMT and lung fibroblast migration

Abstract

AbstractSoluble E‐cadherin (sE‐cad) is an 80 kDa fragment derived from E‐cadherin that is shed from the cell surface through proteolytic cleavage and is a biomarker in various cancers that promotes invasion and migration. Alveolar epithelial destruction, aberrant lung fibroblast migration and inflammation contribute to pulmonary fibrosis. Here, we hypothesized that E‐cadherin plays an important role in lung fibrosis. In this study, we found that E‐cadherin was markedly increased in the bronchoalveolar lavage fluid (BALF) and serum of mice with pulmonary fibrosis and that blocking sE‐cad with HECD‐1, a neutralizing antibody targeting the ectodomain of E‐cadherin, effectively inhibited myofibroblast accumulation and collagen deposition in the lungs after bleomycin (BLM) exposure. Moreover, transforming growth factor‐β (TGF‐β1) induced the shedding of sE‐cad from A549 cells, and treatment with HECD‐1 inhibited epithelial–mesenchymal transition (EMT) stimulated by TGF‐β1. Fc‐E‐cadherin (Fc‐Ecad), which is an exogenous form of sE‐cad, robustly promoted lung fibroblast migration. E‐cadherin participates in bleomycin (BLM)‐induced lung fibrosis by promoting EMT in the alveolar epithelium and fibroblast activation. E‐cadherin may be a novel therapeutic target for lung fibrosis.