title: The involvement of transforming growth factor-beta1 secretion in urotensin II-induced collagen synthesis in neonatal cardiac fibroblasts.
abstract: As the most potent vasoconstrictor in mammals, urotensin II (U II) has recently been demonstrated to play an important role in adverse cardiac remodeling and fibrosis. However, the mechanisms of U II-induced myocardial fibrosis remain to be clarified. We postulated that U II alters transforming growth factor-beta1 (TGF-beta1) expression, and thereby modulates cardiac fibroblast collagen metabolism. Experiments were conducted using cardiac fibroblast from neonatal Wistar rats to determine the expression of TGF-beta1, and the role of U II receptor UT in this process. The functional role of TGF-beta1 and UT in modulating U II effects on type I, III collagen mRNA expression and 3H-proline incorporation was also analyzed. TGF-beta1 gene and protein expression were consistently identified in quiescent cardiac fibroblasts. U II increased the expression of TGF-beta1 mRNA and protein in a time-dependent manner. This effect was UT mediated, because UT antagonist urantide abolished U II-induced TGF-beta1 expression. U II-induced increase in type I, III collagen mRNA expression and 3H-proline incorporation were both inhibited by a specific TGF-beta1 neutralizing antibody and UT receptor antagonist urantide. Hence, our results indicate that TGF-beta1 is upregulated in cardiac fibroblasts by U II via UT and modulates profibrotic effects of U II. These findings provide novel insights into U II-induced cardiac remodeling.
authors.affiliation: Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Qilu Hospital, Shandong University, Jinan, Shandong, China.
authors.forename: Hong-Yan
authors.initials: HY
authors.lastname: Dai
authors.forename: Wei-Qiang
authors.initials: WQ
authors.lastname: Kang
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Yu
authors.forename: Zhen-Hua
authors.initials: ZH
authors.lastname: Li
authors.forename: Meng-Xiong
authors.initials: MX
authors.lastname: Tang
authors.forename: Dong-Ling
authors.initials: DL
authors.lastname: Xu
authors.forename: Chen-Wen
authors.initials: CW
authors.lastname: Li
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Ge
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014579:Urotensins / Q000494:pharmacology*
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D053773:Transforming Growth Factor beta1; D014579:Urotensins; C492079:urotensin II (4-11), Pen(5)-Trp(7)-Orn(8)-; D003094:Collagen; C029677:urotensin II