Abstract
Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle-like cells expressing α-smooth muscle actin (α-SMA) via transforming growth factor-β1/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 α-SMA expression and Smad2 phosphorylation in hASCs. Simvastatin inhibited the SPC-induced α-SMA expression and sustained phosphorylation of Smad2 in hASCs. SPC treatment caused RhoA activation via a simvastatin-sensitive mechanism. The SPC-induced α-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-β1 and pretreatment with either Y27632 or simvastatin inhibited the SPC-induced TGF-β1 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-β1/Smad2 signaling pathway.
Highlights
Smooth muscle cells (SMCs) play an important role in angiogenesis, vessel maintenance, and regulation of blood pressure
We showed that sphingosylphosphorylcholine (SPC) increased the expression levels of α-smooth muscle actin (α-SMA) and other smooth muscle-specific proteins in human adipose tissue-derived mesenchymal stem cells via an autocrine transforming growth factor-β (TGF-β)/Smad2-dependent mechanism (Jeon et al, 2006)
To explore whether statin can affect SPC-induced differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to smooth muscle cells (SMCs), we examined the effect of simvastatin on the SPC-induced expression of smooth muscle-specific markers, including α-SMA and calponin
Summary
Smooth muscle cells (SMCs) play an important role in angiogenesis, vessel maintenance, and regulation of blood pressure. SMCs exhibit a contractile phenotype characterized by high expression of specific contractile proteins, including α-SMA, calponin-1, SM22α, smoothelin, h-caldesmon, and smooth muscle myosin heavy chain (Shanahan et al, 1993; Owens et al, 2004). The phenotypic expression of SMCs is implicated in vascular development as well as in a variety of cardiovascular diseases, including hypertension and atherosclerosis (Liu et al, 2004; Owens et al, 2004). Bone marrow-derived MSCs have been shown to differentiate to smooth muscle cells (SMCs) in response to transforming growth factor-β (TGF-β).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
