title: TGF-β1/FGF-2 signaling mediates the 15-HETE-induced differentiation of adventitial fibroblasts into myofibroblasts.
abstract: BACKGROUND
  Pulmonary adventitial fibroblasts (PAFs) are activated under stress stimuli leading to their differentiation into myofibroblasts, which is involved in vessel remodeling. 15-HETE is known as an important factor in vessel remodeling under hypoxia; however, the role of 15-HETE in PAF phenotypic alteration is not clear.
  
  
  RESULTS
  The effect of 15-HETE on PAF phenotypic alterations was investigated in the present study. PAFs were treated with 15-HETE (0.5 μM) for 24 h, and the myofibroblast marker α-smooth muscle actin (α-SMA) was analyzed. The 15-HETE induced α-SMA expression and cell morphology. 15-HETE upregulated FGF-2 levels in PAFs, and knockdown FGF-2 by siRNAs blocked the enhanced α-SMA expression induced by 15-HETE. p38 kinase was activated, and blocked depressed 15-HETE-induced FGF-2 expression. The downstream of p38 pathway, Egr-1 activation, was also raised by 15-HETE treatment, and silenced Egr-1 suppressed the 15-HETE-induced upregulation of FGF-2. TGF-β1 was upregulated with FGF-2 treatment, and α-SMA expression induced by FGF-2 was inhibited after the cell was transferred with TGF-β1 siRNA. Meanwhile, FGF-2 increased α-SMA expression and improved proliferation, which was associated with p27(kip1) and cyclin E variation.
  
  
  CONCLUSIONS
  The above results suggest that p38/Egr-1 pathway-mediated FGF-2 is involved in 15-HETE-induced differentiation of PAFs into myofibroblasts and cell proliferation.
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Xinyang Road 39, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Daqing Qil Fields General Hospital, Heilongjiang, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Xinyang Road 39, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Guixia
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Xinyang Road 39, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Minggang
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Xinyang Road 39, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Xinyang Road 39, Daqing, Heilongjiang Province, 163319, China.
authors.forename: Yanrui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Harbin Medical University-Daqing, Xinyang Road 39, Daqing, Heilongjiang Province, 163319, China. liym013021@163.com.|Biopharmaceutical Institute of the Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang Province, 150081, China. liym013021@163.com.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
mesh_terms: D000199:Actins / Q000378:metabolism; D063194:Adventitia / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D058628:Myofibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000199:Actins; D016222:Fibroblast Growth Factor 2; D006893:Hydroxyeicosatetraenoic Acids; D053773:Transforming Growth Factor beta1; D048051:p38 Mitogen-Activated Protein Kinases; C498862:Acta2 protein, rat; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid