The Influence of Caldesmon Suppression on Proliferation and Motilities of Vascular Smooth Muscle Cells
- 1 Department of Medical Information, Chongqing Medical University, Chongqing, China
- 2 Department of Biochemistry and Molecular Biology, Chongqing Medical University, Chongqing, China
Abstract
Migration of vascular smooth muscle cells (VSMCs) from the media to intima constitutes a critical step in the development of proliferative vascular diseases. To elucidate the regulatory mechanism of VSMCs motility, the roles of caldesmon (CaD) were investigated previously. CaD is an actin-binding protein dynamically regulating cytoskeleton structure. In this study, the potential role of CaD in mediating proliferation and motility of VSMCs were discussed. First, structural effect of CaD on cytoskeleton integrity was analyzed with CaD knock-down; second, the proliferation of VSMCs was measured in CaD knock-down and control cells; third, the specific role of CaD on VSMCs motilities was evaluated with in vitro migration and invasion assays. We found that CaD is an integral component to maintain cytoskeleton integrity of VSMCs. Our data indicated that CaD suppression does not show significant influence on VSMCs proliferation, but negatively modulates the motilities of VSMCs, and CaD depletion would significantly facilitate migration and invasion of VSMCs.
- Kaperonis, E.A., Liapis, C.D., Kakisis, J.D., Dimitroulis, D., Papavassiliou, V.G., et al. (2006) Inflammation and Chlamydia Pneumoniae Infection Correlate with the Severity of Peripheral Arterial Disease. European Journal of Vascular and Endovascular Surgery, 31, 509-515. http://dx.doi.org/10.1016/j.ejvs.2005.11.022
- Rzucidlo, E.M., Martin, K.A. and Powell, R.J. (2007) Regulation of Vascular Smooth Muscle Cell Differentiation. Journal of Vascular Surgery, 45, A25-A32. http://dx.doi.org/10.1016/j.jvs.2007.03.001
- Gerthoffer, W.T. (2007) Mechanisms of Vascular Smooth Muscle Cell Migration. Circulation Research, 100, 607-621. http://dx.doi.org/10.1161/01.RES.0000258492.96097.47
- Hai, C.M. (2008) Caldesmon as a Therapeutic Target for Proliferative Vascular Diseases. Mini-Reviews in Medicinal Chemistry, 8, 1209-1213. http://dx.doi.org/10.2174/138955708786140981
- Fletcher, D.A. and Mullins, R.D. (2010) Cell Mechanics and the Cytoskel-eton. Nature, 463, 485-492. http://dx.doi.org/10.1038/nature08908
- Wang, C.-L.A. (2001) Caldesmon and Smooth-Muscle Regulation. Cell Biochemistry and Biophysics, 35, 275-288. http://dx.doi.org/10.1385/CBB:35:3:275
- Hayashi, K., Yano, H., Hashihda, T., Takeuchi, R., Takeda, O., Asada, K., Takahashi, E.I., Kato, I. and Sobue, K. (1992) Genomic Structure of the Human Caldesmon Gene. Proceedings of the National Academy of Sciences USA, 89, 12122-12126. http://dx.doi.org/10.1073/pnas.89.24.12122
- Hayashi, K., Fujio, Y., Kato, I. and Sobue, K. (1991) Structural and Functional Relationships between h-and l-Caldesmons. Journal of Biological Chemistry, 266, 355-361.
- Kashiwada, K., Nishida, W., Hayashi, K., Ozawa, K., Yamanaka, Y., Saga, H., Yamashita, T., Tohyama, M., Shimada, S., Sato, K. and Sobue, K. (1997) Coordinate Expression of Alpha-Tropomyosin and Caldesmon Isoforms in Association with Phenotypic Modulation of Smooth Muscle Cells. Journal of Biological Chemistry, 272, 15396-15404. http://dx.doi.org/10.1074/jbc.272.24.15396
- Sobue, K. (1999) Expression Regulation of Smooth Muscle Cellspecific Genes in Association with Phenotypic Modulation. Molecular and Cellular Biochemistry, 190, 105-118. http://dx.doi.org/10.1023/A:1006941621170
- Yoshida, K., Nishida, W., Hayashi, K., Ohkawa, Y., Ogara, A., Aoki, J., et al. (2003) Vascular Remodeling Induced by Naturally Occurring Unsaturated Lysophosphatidic Acid in Vivo. Circulation, 108, 1746-1752. http://dx.doi.org/10.1161/01.CIR.0000089374.35455.F3