Sodium Arsenite Inhibits Lung Fibroblast Differentiation and Pulmonary Fibrosis.

ABSTRACT

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high mortality and poor prognosis. Transforming growth factor (TGF)-ß plays crucial roles in the pathogenesis of IPF. To investigate the role of sodium arsenite (SA) on fibroblast differentiation and pulmonary fibrosis, we checked the effects of SA on TGF-ß-induced normal human lung fibroblasts (NHLFs) differentiation, and the anti-fibrotic effect of SA on bleomycin (BLM)-induced pulmonary fibrosis in mouse. SA treatment significantly inhibits α-smooth muscle actin and fibronectin (FN) expression in TGF-ß treated NHLFs; and SA also inhibits TGF-ß stimulated expression of NADPH oxidase 4 and accumulation of intracellular reactive oxygen species. TGF-ß-induced the phosphorylation of ERK and Smad3 were also blocked by SA. The administration of SA (IP) suppressed BLM-induced lung fibrosis characterized as the inhibition of collagen deposition, TGF-ß accumulation in bronchoalveolar lavage fluid, and the expression of FN and collagen 1a2 in lung tissue. This study revealed that SA inhibits TGF-ß-induced lung fibroblast differentiation and BLM-induced pulmonary fibrosis in mice, suggesting that SA could be a potential therapeutic approach to IPF.