Submitted July 19, 2006
Accepted September 18, 2006
MCP-1 mediates TGF-
-induced angiogenesis by stimulating vascular smooth muscle cell migration
Jing Ma, Qiang Wang, Teng Fei, Jing-Dong Jackie Han, and Ye-Guang Chen*
State Key Lab. of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China
Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
* Corresponding author; email: ygchen{at}tsinghua.edu.cn.
Transforming growth factor-
(TGF-) and its signaling mediators play crucial roles in vascular formation. Our previous microarray analysis has identified monocyte chemoattractant protein-1 (MCP-1) as a TGF- target gene in endothelial cells (ECs). Here, we report that MCP-1 mediates the angiogenic effect of TGF- by recruiting vascular smooth muscle cells (VSMCs) and mesenchymal cells towards ECs. By employing chick chorioallantoic membrane assay, we showed that TGF- promotes the formation of new blood vessels and this promotion is attenuated when MCP-1 activity is blocked by its neutralizing antibody. Wound healing and transwell assays established that MCP-1 functions as a chemoattractant to stimulate migration of VSMCs and mesenchymal 10T1/2 cells toward ECs. Furthermore, the conditioned media from TGF--treated ECs stimulate VSMC migration, and inhibition of MCP-1 activity attenuates TGF--induced VSMC migration toward ECs. Finally, we found that MCP-1 is a direct gene target of TGF- via Smad3/4. Taken together, our findings suggest that MCP-1 mediates TGF--stimulated angiogenesis by enhancing migration of mural cells towards ECs and thus promoting the maturation of new blood vessels.
