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Blood, 1 February 2007, Vol. 109, No. 3, pp. 987-994.
Prepublished online as a Blood First Edition Paper on October 10, 2006; DOI 10.1182/blood-2006-07-036400.
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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
MCP-1 mediates TGF-ß–induced angiogenesis by stimulating vascular smooth muscle cell migration
Jing Ma1,
Qiang Wang1,
Teng Fei1,
Jing-Dong Jackie Han2, and
Ye-Guang Chen1
From the1 State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China; and
2 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China
Transforming growth factor-ß (TGF-ß) and its signaling mediators play crucial roles in vascular formation. Our previous microarray analysis identified monocyte chemoattractant protein-1 (MCP-1) as a TGF-ß target gene in endothelial cells (ECs). Here, we report that MCP-1 mediates the angiogenic effect of TGF-ß by recruiting vascular smooth muscle cells (VSMCs) and mesenchymal cells toward ECs. By using a chick chorioallantoic membrane assay, we show that TGF-ß 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-ß–treated ECs stimulate VSMC migration, and inhibition of MCP-1 activity attenuates TGF-ß–induced VSMC migration toward ECs. Finally, we found that MCP-1 is a direct gene target of TGF-ß via Smad3/4. Taken together, our findings suggest that MCP-1 mediates TGF-ß–stimulated angiogenesis by enhancing migration of mural cells toward ECs and thus promoting the maturation of new blood vessels.
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