Mechanochemical alterations in lung cells during fibrogenesis

Abstract

Idiopath pulmonary fibrosis (IPF) is a usually fatal disease associated with hardening of the lung tissue, epithelial injury and abnormal wound healing. Myo_broblasts are cells with smooth muscle like features and are believed to promote abnormal extracellular matrix (ECM) deposition, perpetuated scarring and loss of tissue function during fibrosis. These cells seem to arise either from epithelial cells via transforming growth factor (TGFß1) induced epithelial to mesenchymal transition (EMT) or from the activation of resident fibroblasts through TGFß1 mediated fibroblast to myofibroblast transition (FMT). We treated with TGFß1 three human lung epithelial cell lines (H441, A549, H1975) and primary lung fibroblasts from three healthy patients and from three IPF patients. We used immunouorescence techniques in order to quantify the expression of various cytoskeletal proteins (F-actin, alpha smooth muscle actin and vimentin) in both treated and untreated cells. We also used atomic force microscopy to measure the Young modulus of the cells. When treated with TGFß1, epithelial cells adopted a mesenchymal morphology and displayed indicators of EMT. TGFß1 stimulated fibroblasts acquired a myofibroblast phenotype, supporting the hypothesis of resident fibroblast activation through TGFß1 induced FMT.