Exp Mol Med.
2012 Feb;44(2):159-166. 10.3858/emm.2012.44.2.011.
Simvastatin inhibits sphingosylphosphorylcholine-induced differentiation of human mesenchymal stem cells into smooth muscle cells
- Affiliations
-
- 1Medical Research Center for Ischemic Tissue Regeneration, School of Medicine, Pusan National University, Yangsan 626-870, Korea. jhkimst@pusan.ac.kr
- 2Department of Physiology, School of Medicine, Pusan National University, Yangsan 626-870, Korea.
- 3Department of Dermatology, School of Medicine, Pusan National University, Yangsan 626-870, Korea.
- 4Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan 626-770, Korea.
- KMID: 1120134
- DOI: http://doi.org/10.3858/emm.2012.44.2.011
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.
Keyword
MeSH Terms
-
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
- Full Text Links
-
- Actions
-
Cited
- CITED
-
- Close
- Share
-
- Similar articles
-
- Osteogenic potential of adult stem cells from human maxillary sinus membrane by Simvastatin in vitro: preliminary report
- Effects of Damaged Human Corneal Epithelial Cells on Differentiation of Human Mesenchymal Stem Cell
- Differentiation of Osteoblast Progenitor Cells from Human Umbilical Cord Blood
- Concise Review: Differentiation of Human Adult Stem Cells Into Hepatocyte-like Cells In vitro
- Stem Cell Therapy for Erectile Dysfunction
