title: Mechanical stretching stimulates collagen synthesis via down-regulating SO2/AAT1 pathway.
abstract: The aim of the study was to investigate the role of endogenous sulfur dioxide (SO2)/ aspartate aminotransferase 1 (AAT1) pathway in stretch-induced excessive collagen expression and its mechanism. The mechanical stretch downregulated SO2/AAT1 pathway and increased collagen I and III protein expression. Importantly, AAT1 overexpression blocked the increase in collagen I and III expression, transforming growth factor-β1 (TGF- β1) expression and phosphorylation of Smad2/3 induced by stretch, but AAT1 knockdown mimicked the increase in collagen I and III expression, TGF- β1 expression and phosphorylation of Smad2/3 induced by stretch. Mechanistically, SB431542, a TGF-β1/Smad2/3 inhibitor, eliminated excessive collagen I and III accumulation induced by AAT1 knockdown, stretch or stretch plus AAT1 knockdown. In a rat model of high pulmonary blood flow-induced pulmonary vascular collagen accumulation, AAT1 expression and SO2 content in lung tissues of rat were reduced in shunt rats with high pulmonary blood flow. Supplement of SO2 derivatives inhibited activation of TGF- β1/Smad2/3 pathway and alleviated the excessive collagen accumulation in lung tissues of shunt rats. The results suggested that deficiency of endogenous SO2/AAT1 pathway mediated mechanical stretch-stimulated abnormal collagen accumulation via TGF-β1/Smad2/3 pathway.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Wen
authors.initials: W
authors.lastname: Yu
authors.affiliation: Anzhen Hospital, Capital Medical University, Beijing 100020, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: University of California, San Diego, La Jolla, California, 92093, United States of America.
authors.forename: Selena
authors.initials: S
authors.lastname: Chen
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 Cardiovascular Pediatrics, Capital Institute of Pediatrics, Beijing 100020, P. R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pediatrics, Tianjin Fifth Centre Hospital, Tianjin 300450, P. R. China.
authors.forename: Cuiping
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, The Hospital of Shunyi District Beijing, Beijing 101300, P. R. China.
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing 100034, P. R. China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Anzhen Hospital, Capital Medical University, Beijing 100020, P. R. China.|Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education (2014XXGB02).
authors.forename: Jie
authors.initials: J
authors.lastname: Du
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.|Anzhen Hospital, Capital Medical University, Beijing 100020, P. R. China.
authors.forename: Hongfang
authors.initials: H
authors.lastname: Jin
mesh_terms: D000818:Animals; D024443:Aspartate Aminotransferase, Cytoplasmic / Q000235:genetics / Q000378:metabolism*; D003094:Collagen / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D055785:Gene Knockdown Techniques; D008168:Lung / Q000166:cytology / Q000378:metabolism; D040542:Mechanotransduction, Cellular; D051381:Rats; D015398:Signal Transduction; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D013458:Sulfur Dioxide / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D051899:Smad2 Protein; D051900:Smad3 Protein; D053773:Transforming Growth Factor beta1; D013458:Sulfur Dioxide; D003094:Collagen; D024443:Aspartate Aminotransferase, Cytoplasmic