title: Urotensin upregulates transforming growth factor-β1 expression of asthma airway through ERK-dependent pathway.
abstract: Airway smooth muscle cells (ASMCs) play a key role in the process of asthma airway remodeling. Urotensin II (UII) and transforming growth factor (TGF)-β are potent mitogens for ASMCs proliferation. The study was aimed to determine whether UII-upregulated TGF-β-mediated ASMCs proliferation and extracellular signal-regulated kinase (ERK) was required for such an effect. OVA-sensitized rats were challenged to induce asthma. Lung morphology and airway dynamic parameters were monitored. ASMCs from control and asthma rats were purified for the measurement of UII and TGF-β1 expression. In vitro experiments were conducted to determine the direct effect of UII on TGF-β1 expression by ASMCs. Finally, U0126, an ERK inhibitor was used to examine the role of ERK pathway in UII mediated TGF-β1 upregulation. We found that both UII and TGF-β1 were upregulated in asthma lung tissues. In vitro study on ASMCs further revealed that UII may render its effect on ASMCs cells through the upregulation of TGF-β1. Data also supported the conclusion that ERK pathway was required, but not sufficient in UII-induced TGF-β1 upregulation. The current study provides new evidence that UII is involved in the TGF-β mediated mitogenic effect on ASMCs. UII, at least partially, uses ERK pathway to render such effect.
authors.affiliation: Department of Pediatric Pulmonology, The Second Affiliated Hospital & Yuying Children's Hospital, Wenzhou Medical College, Wenzhou 325027, Zhejiang, China.
authors.forename: Wei-Xi
authors.initials: WX
authors.lastname: Zhang
authors.forename: Ya-Feng
authors.initials: YF
authors.lastname: Liang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Nie
authors.forename: Lei
authors.initials: L
authors.lastname: Chong
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Chun
authors.initials: C
authors.lastname: Chen
authors.forename: Chang-Chong
authors.initials: CC
authors.lastname: Li
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010047:Ovalbumin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D014579:Urotensins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002070:Butadienes; D009570:Nitriles; D053773:Transforming Growth Factor beta1; C113580:U 0126; D014579:Urotensins; D010047:Ovalbumin; C029677:urotensin II; D048049:Extracellular Signal-Regulated MAP Kinases