Galectin-3 contributes to vascular fibrosis in monocrotaline-induced pulmonary arterial hypertension rat model.

Abstract

Galectin-3 (Gal-3) plays a critical role in vascular inflammation and fibrosis. The role of TGF-β1 in mediating pulmonary vascular fibrosis is well documented; thus, we suspected that Gal-3 could be an important factor in TGF-β1-induced fibrosis in pulmonary adventitial fibroblasts (PAFs). We treated rats with monocrotaline (MCT) and cultured PAFs with TGF-β1 to stimulate fibrosis. We found that MCT injection induced vessel thickening and extracellular matrix deposition in vivo. TGF-β1 stimulated the production of collagen and fibronectin (Fn) protein in vitro. TGF-β1 promoted the expression of Gal-3 and its translocation, while silencing Gal-3 reduced Col-1a deposition. Blockage of STAT3 decreased the expression of Gal-3 induced by TGF-β1. Gal-3 increased Col-1a accumulation and downregulated matrix metallopeptidase 9 (MMP-9) expression in PAFs, but it did not affect Fn expression. These findings demonstrate that Gal-3 is required for TGF-β1-stimulated vascular fibrosis via a STAT3 signaling cascade and that MMP-9 is also involved in TGF-β1/Gal-3-induced vascular fibrosis.