title: Phosphatidylinositol-3-kinase signaling mediates vascular smooth muscle cell expression of periostin in vivo and in vitro.
abstract: OBJECTIVE
  Periostin is dramatically upregulated in rat carotid arteries after balloon injury. The objective of the present study was to understand mechanisms underlying periostin upregulation in balloon-injured rat carotid arteries and in cultured vascular smooth muscle cells (VSMCs).
  
  
  RESULTS
  Periostin protein was strongly expressed at 3 days (in the medial SMCs) and 7 days (in the neointima) after injury. It was also abundantly expressed in the neointima in the late phase (at 14 and 28 days) after injury. Periostin upregulation was mediated through PI-3-kinase-dependent signaling pathway. In vivo, wortmannin, a PI-3-kinase inhibitor, inhibited balloon injury-induced Akt phosphorylation and periostin mRNA expression. In vitro, periostin mRNA expression in cultured VSMCs was stimulated by growth factors (transforming growth factor-beta1 (TGF-beta1), fibroblast growth factors (FGFs), PDGF-BB, and angiotensin II). This stimulatory effect was inhibited by the PI-3-kinase inhibitor LY294002. Further, periostin protein was mostly located in the cytoplasma of VSMCs in culture and abundantly secreted into the culture medium (CM) after stimulation with FGF-2, which significantly promoted VSMC migration in vitro. Immunodepletion of periostin from the VSMC-CM or blockade of periostin function with an anti-periostin antibody significantly reduced VSMC migration.
  
  
  CONCLUSIONS
  Upregulation of periostin expression in rat carotid arteries following balloon injury and in cultured VSMCs after stimulation by growth factors is mediated through PI-3-kinase-dependent signaling pathway. Periostin protein secreted by VSMCs plays a significant role in regulating VSMC migration in vitro.
authors.affiliation: Cardiovascular Division of Internal Medicine and Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, USA. ghli@med.unc.edu
authors.forename: Guohong
authors.initials: G
authors.lastname: Li
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.forename: John M
authors.initials: JM
authors.lastname: Sanders
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.forename: Meiru
authors.initials: M
authors.lastname: Dai
authors.forename: Lan Bo
authors.initials: LB
authors.lastname: Chen
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.forename: Coleen A
authors.initials: CA
authors.lastname: McNamara
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Sarembock
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000378:metabolism*; D002404:Catheterization / Q000009:adverse effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D036341:Intercellular Signaling Peptides and Proteins; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin; C512836:Postn protein, rat