title: STAT3-mediated MMP-2 expression is required for 15-HETE-induced vascular adventitial fibroblast migration.
abstract: OBJECTIVE
  Vascular adventitial fibroblasts (VAFs) migration was involved in neointima formation, and increased 15-HETE levels contributed to vascular remodeling. However, how 15-HETE-induced VAF migration was not clear.
  
  
  RESULTS
  15-HETE-stimulated VAF phenotypic changes and migration as measured by the wound healing assay required STAT3 phosphorylation. JNK1 and CREB inhibition blocked 15-HETE-induced STAT3 activation and VAF changes. 15-HETE-induced MMP-2 expression and secretion were analyzed by Western blot and ELISA, respectively. MMP-2 knockdown blocked VAF migration and phenotypic alterations. JNK1, STAT3 and CREB blockade suppressed 15-HETE-induced MMP-2 expression in VAFs. MMP-2 promoter activity was assessed by chromatin immunoprecipitation using anti-STAT3 antibodies, which demonstrated that STAT3 was essential for 15-HETE-induced MMP-2 expression. Rats that suffered from hypoxia injury with or without treatment were examined. Pulmonary artery remodeling was obviously observed, and even the media was broken. MMP-2-positive staining was observed in the adventitia and intima. MMP-2 Serum secretion was enhanced as detected by ELISA, and MMP-2 and α-SMA protein expressions were increased after inducing hypoxia in the rats, which was restored in rats that had been administrated with NDGA.
  
  
  CONCLUSIONS
  These results reveal that STAT3-mediated MMP-2 expression is required for 15-HETE induced-VAF migration.
authors.affiliation: Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang Province 163319, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang Province 163319, China; Biopharmaceutical Institute of the Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang Province 150081, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang Province 163319, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang Province 163319, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang Province 163319, China.
authors.forename: Minggang
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang Province 163319, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Department of Pharmacology, Harbin Medical University - Daqing, Daqing, Heilongjiang Province 163319, China; Biopharmaceutical Institute of the Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang Province 150081, China. Electronic address: dalingz@yahoo.com.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D063194:Adventitia / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002465:Cell Movement; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism*; D008168:Lung / Q000098:blood supply*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D058426:Neointima / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D015854:Up-Regulation; D066253:Vascular Remodeling
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D006893:Hydroxyeicosatetraenoic Acids; D050796:STAT3 Transcription Factor; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D048055:Mitogen-Activated Protein Kinase 8; D020778:Matrix Metalloproteinase 2
keywords: 15-HETE; Adventitia fibroblast; MMP-2; Migration; STAT3