Simvastatin inhibits sphingosylphosphorylcholine-induced differentiation of human mesenchymal stem cells into smooth muscle cells.
10.3858/emm.2012.44.2.011
- Author:
Kyung Hye KIM
1
;
Young Mi KIM
;
Mi Jeong LEE
;
Hyun Chang KO
;
Moon Bum KIM
;
Jae Ho KIM
Author Information
1. Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Korea. jhkimst@pusan.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
cell differentiation;
mesenchymal stem cells;
myocytes, smooth muscle;
rhoA GTP-binding protein;
simvastatin;
sphingosine phosphorylcholine;
transforming growth factor beta1
- MeSH:
Amides/pharmacology;
Blotting, Western;
Cell Differentiation/*drug effects;
Cells, Cultured;
Enzyme-Linked Immunosorbent Assay;
Humans;
Immunohistochemistry;
Mesenchymal Stem Cells/*cytology/*drug effects;
Myocytes, Smooth Muscle/*cytology/*drug effects;
Phosphorylcholine/*analogs & derivatives/pharmacology;
Pyridines/pharmacology;
Simvastatin/*pharmacology;
Sphingosine/*analogs & derivatives/pharmacology;
rhoA GTP-Binding Protein/antagonists & inhibitors/metabolism
- From:Experimental & Molecular Medicine
2012;44(2):159-166
- CountryRepublic of Korea
- Language:English
-
Abstract:
Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle-like cells expressing alpha-smooth muscle actin (alpha-SMA) via transforming growth factor-beta1/Smad2- and RhoA/Rho kinase-dependent mechanisms. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have been known to have beneficial effects in the treatment of cardiovascular diseases. In the present study, we examined the effects of simvastatin on the SPC-induced alpha-SMA expression and Smad2 phosphorylation in hASCs. Simvastatin inhibited the SPC-induced alpha-SMA expression and sustained phosphorylation of Smad2 in hASCs. SPC treatment caused RhoA activation via a simvastatin-sensitive mechanism. The SPC-induced alpha-SMA expression and Smad2 phosphorylation were abrogated by pretreatment of the cells with the Rho kinase inhibitor Y27632 or overexpression of a dominant negative RhoA mutant. Furthermore, SPC induced secretion of TGF-beta1 and pretreatment with either Y27632 or simvastatin inhibited the SPC-induced TGF-beta1 secretion. These results suggest that simvastatin inhibits SPC-induced differentiation of hASCs into smooth muscle cells by attenuating the RhoA/Rho kinase-dependent activation of autocrine TGF-beta1/Smad2 signaling pathway.
