MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth muscle cell migration.
Transforming growth factor-beta (TGF-beta) and its signaling mediators play crucial roles in vascular formation. Our previous microarray analysis identified monocyte chemoattractant protein-1 (MCP-1) as a TGF-beta target gene in endothelial cells (ECs). Here, we report that MCP-1 mediates the angiogenic effect of TGF-beta by recruiting vascular smooth muscle cells (VSMCs) and mesenchymal cells toward ECs. By using a chick chorioallantoic membrane assay, we show that TGF-beta 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-beta-treated ECs stimulate VSMC migration, and inhibition of MCP-1 activity attenuates TGF-beta-induced VSMC migration toward ECs. Finally, we found that MCP-1 is a direct gene target of TGF-beta via Smad3/4. Taken together, our findings suggest that MCP-1 mediates TGF-beta-stimulated angiogenesis by enhancing migration of mural cells toward ECs and thus promoting the maturation of new blood vessels.
Ma
Jing
J
State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China.
Wang
Qiang
Q
Fei
Teng
T
Han
Jing-Dong Jackie
JD
Chen
Ye-Guang
YG
D002450:Cell Communication; D002465:Cell Movement; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000502:physiology*; D002630:Chemotactic Factors; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D002630:Chemotactic Factors; D016212:Transforming Growth Factor beta