title: 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.
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, People's Republic of China.|Department of Physiology, Harbin Medical University-Daqing, Daqing, Heilongjiang Province, 163319, People's Republic of China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Kailuan General Hospital, Tangshan, Hebei Province, 063000, People's Republic of China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, People's Republic of China.
authors.forename: Jinbo
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Guan
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, People's Republic of China.
authors.forename: Minggang
authors.initials: M
authors.lastname: Chen
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, People's Republic of China.|Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, People's Republic of China.|Department of Pharmacology, Harbin Medical University-Daqing, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D037502:Galectin 3 / Q000378:metabolism*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D016686:Monocrotaline / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014652:Vascular Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology
chemical_list: D037502:Galectin 3; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D016686:Monocrotaline; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: Galectin-3; TGF-β1; fibrosis; pulmonary adventitial fibroblasts