TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis.

Abstract

The differentiation of fibroblasts to myofibroblasts is critical for the development of idiopathic pulmonary fibrosis (IPF). T-cell lymphoma invasion and metastasis 1 (TIAM1) is known to be associated with amyotrophic lateral sclerosis 1 and colorectal cancer; however, its role in IPF is unclear. The aim of the present study was to investigate the expression and roles of TIAM1 in lung fibroblasts during pulmonary fibrosis. It was demonstrated that TIAM1 expression was significantly increased in fibrotic lung tissue and lung fibroblasts from bleomycin (BLM)-treated mice compared with control mice (P<0.05). TIAM1 expression and differentiation were significantly upregulated in human lung fibroblasts challenged with transforming growth factor-β (TGF-β) compared with unchallenged cells (P<0.05). Furthermore, inhibition of the nuclear factor (NF)-κB signaling pathway significantly attenuated TGF-β-induced TIAM1 expression and decreased fibroblast differentiation in human lung fibroblasts (P<0.05). Similarly, overexpression of TIAM1 significantly inhibited TGF-β-induced fibroblast differentiation, as indicated by decreased expression of fibronectin and α-smooth muscle actin (SMA; P<0.05). The results of the present study also demonstrated that TIAM1 knockdown increased TGF-β-induced fibroblast differentiation (P<0.05). These findings suggest that TIAM1 expression is associated with lung fibroblast differentiation in pulmonary fibrosis via an NF-κB-dependent pathway, and that TIAM1 inhibits lung fibroblast differentiation in pulmonary fibrosis.