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Tissue-Specific Stem Cells
Article first published online: 5 JAN 2009
Copyright © 2008 AlphaMed Press
Volume 27, Issue 1, pages 191–199, January 2009
How to Cite
Kim, M. R., Jeon, E. S., Kim, Y. M., Lee, J. S. and Kim, J. H. (2009), Thromboxane A2 Induces Differentiation of Human Mesenchymal Stem Cells to Smooth Muscle-Like Cells. STEM CELLS, 27: 191–199. doi: 10.1634/stemcells.2008-0363
Author contributions: M.R.K.: conception and design, collection and assembly of data, data analysis and interpretation, manuscript writing; E.S.J. and Y.M.K.: collection and assembly of data, data analysis and interpretation; J.S.L.: provision of study material or patients, data analysis and interpretation; J.H.K.: conception and design, financial support, data analysis and interpretation, manuscript writing, final approval of manuscript; M. R. K. and E. S. J. contributed equally to this work.
Disclosure of potential conflicts of interest is found at the end of this article.
First published online in STEM CELLSExpress October 9, 2008.
- Issue published online: 5 JAN 2009
- Article first published online: 5 JAN 2009
- Manuscript Accepted: 30 SEP 2008
- Manuscript Received: 29 APR 2008
- Medical Research Center program of the Ministry of Science and Technology/Korea Science and Engineering Foundation. Grant Number: R13-2005-009
- Korea Research Foundation. Grant Number: KRF-2007-521-C00225
- Thromboxane A2, Mesenchymal stem cells;
- Smooth muscle cells
Thromboxane A2 (TxA2) is involved in smooth muscle contraction and atherosclerotic vascular diseases. Accumulating evidence suggests a pivotal role for mesenchymal stem cells (MSCs) in vascular remodeling. In the present study, we demonstrate for the first time that the TxA2 mimetic U46619 induces differentiation of human adipose tissue-derived MSCs (hADSCs) to smooth muscle-like cells, as demonstrated by increased expression of smooth muscle-specific contractile proteins such as α-smooth muscle actin (α-SMA), calponin, smoothelin, and smooth muscle-myosin heavy chain. Using an in vitro collagen gel lattice contraction assay, we showed that U46619-induced expression of the contractile proteins was associated with increased contractility of the cells. U46619 increased the intracellular Ca2+ concentration in hADSCs and pretreatment of the cells with the thromboxane receptor antagonist SQ29548 or the calmodulin (CaM) inhibitor W13 abrogated the U46619-induced α-SMA expression and contractility, suggesting a pivotal role of Ca2+/CaM in the U46619-stimulated smooth muscle differentiation of hADSCs. In addition, U46619 elicited activation of RhoA in hADSCs, and pretreatment of the cells with the Rho kinase-specific inhibitor Y27632 or overexpression of the dominant-negative mutants of RhoA and Rho kinase blocked U46619-stimulated α-SMA expression and contractility. Furthermore, U46619 induced phosphorylation of myosin light chain (MLC) through CaM/MLC kinase- and Rho kinase-dependent pathways, and the MLC kinase inhibitor ML-7 abrogated U46619-induced α-SMA expression and contractility. These results suggest that U46619 induces differentiation of hADSCs to contractile smooth muscle-like cells through CaM/MLCK- and RhoA-Rho kinase-dependent actin polymerization. STEM CELLS2009;27:191–199