Roles of periostin in proliferation and migration of vascular smooth muscle cells and the effect of atorvastatin on them.
10.3969/j.issn.1672-7347.2012.07.007
- Author:
Jingle LI
1
;
Wenguang YAN
;
Jiangang WANG
;
Wenpeng TAN
;
Yu ZHOU
;
Kan YANG
Author Information
1. Department of Cardiology, Central South University, Changsha, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Atorvastatin;
Cell Adhesion Molecules;
genetics;
metabolism;
Cell Movement;
drug effects;
Cell Proliferation;
drug effects;
Heptanoic Acids;
pharmacology;
Male;
Muscle, Smooth, Vascular;
cytology;
metabolism;
Myocytes, Smooth Muscle;
metabolism;
Primary Cell Culture;
Pyrroles;
pharmacology;
RNA, Messenger;
genetics;
metabolism;
Rats;
Rats, Sprague-Dawley;
Signal Transduction;
Transforming Growth Factor beta1;
pharmacology;
rho-Associated Kinases;
metabolism
- From:
Journal of Central South University(Medical Sciences)
2012;37(7):689-694
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the expression of periostin in in vitro cultured vascular smooth muscle cells (VSMCs) induced by TGF-β1 and the relationship between periostin expression and the migration and proliferation of the VSMCs. Further, to investigate the effects of atorvastatin on the above-mentioned processes and the molecular mechanisms of atorvastatin inhibition of TGF-β1- induced periostin production.
METHODS:Rat aorta smooth muscle cells were cultivated by the method of tissue explants adherence. Cells of generation 3 to 6 were used as the experimental system. Primary cultured rat vascular smooth muscle cells were treated by TGF-β1 and different concentrations of atorvastatin,Y-2763 (Rho kinase inhibitor), or atorvastatin plus MVA for 24 hours. The expression of periostin was measured by RT-PCR and Western blot. A Boyden chamber assay was used to measure cell migration, and an MTT test was used to measure cell proliferation.
RESULTS:Periostin expression in rat VSMCs stimulated by TGF-β1 increased significantly (4.158 ± 0.515 vs 0.385 ± 0.031), VSMC migration(25 ± 4 vs 8 ± 2) and proliferation (0.85 ± 0.06 vs 0.32 ± 0.03) also increased significantly. Atorvastatin significantly inhibited TGF-β1-induced periostin production in rat VSMCs, as well as VSMC migration and proliferation, in a dose-dependent manner. Rho kinase inhibitor Y-27632 significantly inhibited TGF-β1-induced periostin production in rat VSMCs (2.082 ± 0.245). The inhibitory effect of atorvastatin on periostin upregulation induced by TGF-β1 was reversed by mevalonate (3.838 ± 0.326).
CONCLUSION:Periostin can promote rat VSMC migration and proliferation. Atorvastatin inhibition of periostin expression induced by TGF-β1 in VSMCs may be exerted by inhibition of the production of MVA and other isoprene compounds and by blocking the Rho/Rho kinase signaling pathway.