Transforming growth factor-β3 induced rat bone marrow-derived mesenchymal stem cells differentiation into smooth muscle cells by activating Myocardin

Lin-Lin Ma, Nan Wang, Zhen Zhou, Jun-Yun Zhang, Xue-Gang Luo, Yong Jiang, Tong-Cun Zhang

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DOI: 10.4236/jbise.2009.28095                

Abstract

Bone marrow mesenchymal stem cells (MSCs) can differentiate into smooth muscle cells (SMCs) and have tremendous potential for cell therapy and tissue engineering. In this study, to understand the effects of TGF-β3 on rat bone marrow-derived MSCs and the underlying molecular mechanism of this differentiation process, we investigated that the changes of myocardin-related transcription factors (MRTFs) at the transcriptional level after rat MSCs were treated with TGF-β3. The results showed that TGF-β3 increased the expression of contractile genes, such as SM22, smooth muscle-myosin heavy chain (SM- MHC), SM-α-actin in MSCs. When TGF-β3 induced MSCs differentiation into SMCs, myocardin and MRTF-A were activated. The data indicated that TGF-β3 induced rat bone marrow-derived MSCs differentiation into SMCs by activating mypcardin and MRTF-A.

Keywords

Mesenchymal Stem Cells; Smooth Muscle Cells; TGF-β; MRTFs

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	J. Y. Lai, C. Y. Yoon, J. J. Yoo, T. Wulf, and A. Atala. (2002) Phenotypic and functional characterization of in bivo tissue engineered smooth muscle from normal and pathological bladders. J. Urol., Sugar Land, 168, 1853–1857.
[2]	D. Orlic, J. Kajstura, S. Chimenti, I. Jakoniuk, S. M. Anderson, B. Li, et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature, 410, 701–705.
[3]	M. F. Pittenger, A. M. Mackay, S. C. Beck, R. K. Jaiswal, R. Douglas, J. Mosca, et al., (1999) Multilineage poten- tial of adult humanmesenchymal stem cells. Science, 284, 143–147.
[4]	S. Davani, A. Marandin, N. Mersin, B. Royer, B. Kantelip, P. Herve, et al. (2003) Mesenchymal progenitor cells differentiate into an endothelial pheno- type, enhance vascular density, and improve heart fun- ction in a rat cellular cardiomyoplasty model. Circulation, 108, II253–II258.
[5]	B. Kinner, J. M. Zaleskas, M. Spector. (2002) Regulation of smooth muscle actin expression and contraction in adult human mesenchymal stem cells. Exp. Cell Res, 278, 72–83.
[6]	E. S. Jeon, H. J. Moon, M. J. Lee, H. Y. Song, Y. M. Kim, Y. C. Bae, et al., (2006) Sphingosylphosphoryl- choline induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through A TGF- beta-dependent mechanism. J Cell Sci., 119, 4994–5005.
[7]	G. C. Pipes, E. E. Creemers, E. N. Olson. (2006) The myocardin family of transcriptional coactivators: versatile regulators of cell growth, migration, and myogenesis. Genes Dev., 20, 1545–1556.
[8]	C. D. Li, W. Y. Zhang, H. L. Li, X. X. Jiang, Y. Zhang, P. H. Tang, et al. (2005) Mesenchymal stem cells derived from human placenta suppress allogeneic umbilical cord blood lymphocyte proliferation. Cell Res., 15, 539–547.
[9]	P. Price and T. J. McMillan. (1990) Use of the tetrazolium assay in measuring the response of human tumor cells to ionizing radiation. Cancer Res., 50, 1392–1396.
[10]	N. Kobayashi, T. Yasu, H. Ueba, M. Sata, S. Hashimoto, M. Kuroki, et al. (2004) Mechanical stress promotes the epression of smooth muscle-like properties in marrow stromal cells. Exp. Hematol., 32, 1238–1245.
[11]	J. J. Ross, Z. Hong, B. Willenbring, L. Zeng, B. Isenberg, E. H. Lee, et al. (2006) Cytokine-induced differentia- tion of multipotent adult progenitor cells into functional smooth muscle cells, J Clin Invest., 116, 3139–3149.
[12]	S. G. Ball, A. C. Shuttleworth, C. M. Kielty. (2004) Direct cell contact influences bone marrow mesen- chymal stem cell fate. Int. J. Biochem, Cell Biol., 36, 714–727.
[13]	S. Sinha, M. H. Hoofnagle, P. A. Kingston, M. E. McCanna, G. K. Owens. (2004) Transforming growth factor-β1 signaling contributes to development of smooth muscle cells from embryonic stem cells. Am. J. Physiol. Cell. Physiol., 287, C1560–C1568.