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Galectin‐3 contributes to vascular fibrosis in monocrotaline‐induced pulmonary arterial hypertension rat model
Author(s) -
Wang Xiaoyan,
Wang Yanli,
Zhang Jinbo,
Guan Xue,
Chen Minggang,
Li Yumei,
Zhang Li
Publication year - 2017
Publication title -
journal of biochemical and molecular toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.526
H-Index - 58
eISSN - 1099-0461
pISSN - 1095-6670
DOI - 10.1002/jbt.21879
Subject(s) - fibronectin , fibrosis , galectin 3 , extracellular matrix , transforming growth factor , pulmonary fibrosis , chemistry , matrix metalloproteinase , inflammation , cancer research , pulmonary hypertension , medicine , pathology , biochemistry
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.