Phosphatidylinositol-3-kinase signaling mediates vascular smooth muscle cell expression of periostin in vivo and in vitro

Li, Guohong; Oparil, Suzanne; Sanders, John M.; Zhang, Lin; Dai, Meiru; Chen, Lan Bo; Conway, Simon J.; McNamara, Coleen A.; Sarembock, Ian J.

doi:10.1016/j.atherosclerosis.2005.11.002

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Volume 188, Issue 2 , Pages 292-300, October 2006

Phosphatidylinositol-3-kinase signaling mediates vascular smooth muscle cell expression of periostin in vivo and in vitro

Guohong Li
- Cardiovascular Division of Internal Medicine and Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, United States
- Corresponding author. Present address: Department of Cell and Molecular Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States. Tel.: +1 919 843 4586; fax: +1 919 843 4585.
Suzanne Oparil
- Vascular Biology and Hypertension Program, University of Alabama at Birmingham, Birmingham, AL, United States
John M. Sanders
- Cardiovascular Division of Internal Medicine and Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, United States
Lin Zhang
- Cardiovascular Division of Internal Medicine and Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, United States
Meiru Dai
- Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Lan Bo Chen
- Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, United States
Simon J. Conway
- Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States
Coleen A. McNamara
- Cardiovascular Division of Internal Medicine and Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, United States
Ian J. Sarembock
- Cardiovascular Division of Internal Medicine and Cardiovascular Research Center, University of Virginia Health System, Charlottesville, VA, United States

Received 20 June 2005; received in revised form 17 October 2005; accepted 1 November 2005. published online 05 December 2005.

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).

Methods and 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-β1 (TGF-β1), 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.

Keywords: Periostin, PI-3-kinase, Smooth muscle, Migration