title: Endogenous sulfur dioxide alleviates collagen remodeling via inhibiting TGF-β/Smad pathway in vascular smooth muscle cells.
abstract: The study was designed to investigate the role of endogenous sulfur dioxide (SO2) in collagen remodeling and its mechanisms in vascular smooth muscle cells (VSMCs). Overexpression of endogenous SO2 synthase aspartate aminotransferase (AAT) 1 or 2 increased SO2 levels and inhibited collagen I and III expressions induced by transforming growth factor (TGF)-β1 in VSMCs. In contrast, AAT1 or AAT2 knockdown induced a severe collagen deposition in TGF-β1-treated VSMCs. Furthermore, AAT1 or AAT2 overexpression suppressed procollagen I and III mRNA, upregulated matrix metalloproteinase (MMP)-13 expression, downregulated tissue inhibitors of MMP-1 level, and vice versa. Mechanistically, AAT1 or AAT2 overexpression inhibited phosphorylation of type I TGF-β receptor (TβRI) and Smad2/3 in TGF-β1-stimulated VSMCs. Whereas SB431542, an inhibitor of TGF-β1/Smad signaling pathway, attenuated excessive collagen deposition induced by AAT knockdown. Most importantly, ectopically expressing AAT or exogenous addition of 100 μM SO2 blocked AAT deficiency-aggravated collagen accumulation in TGF-β1-stimulatd VSMCs, while no inhibition was observed at 100 μM ethyl pyruvate. These findings indicated that endogenous SO2 alleviated collagen remodeling by controlling TGF-β1/TβRI/Smad2/3-mediated modulation of collagen synthesis and degradation.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Yaqian
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Zhizhou
authors.initials: Z
authors.lastname: Shen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, P. R. China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Capital Medical University Shijitan Hospital, Beijing 100038, P. R. China.
authors.forename: Shuxu
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Geng
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Green Chemistry and Technology, Ministry of Education, College of Chemistry, Sichuan University, Chengdu, 610064, P. R. China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Physiology and Pathophysiology, Peking University Health Science Centre, Beijing 100191, P. R. China.|Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, P. R. China.
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.|Key Laboratory of Molecular Cardiology, Ministry of Education, Beijing 100191, P. R. China.
authors.forename: Junbao
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D000066630:Ectopic Gene Expression; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D059748:Proteolysis; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D013458:Sulfur Dioxide / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D013458:Sulfur Dioxide; D019289:Pyruvic Acid; D003094:Collagen