PMID- 17032917 OWN - NLM STAT- MEDLINE DCOM- 20070306 LR - 20220408 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 109 IP - 3 DP - 2007 Feb 1 TI - MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth muscle cell migration. PG - 987-94 AB - 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. FAU - Ma, Jing AU - Ma J AD - State Key Laboratory of Biomembrane and Membrane Biotechnology, Department of Biological Sciences and Biotechnology, Tsinghua University, Beijing, China. FAU - Wang, Qiang AU - Wang Q FAU - Fei, Teng AU - Fei T FAU - Han, Jing-Dong Jackie AU - Han JD FAU - Chen, Ye-Guang AU - Chen YG LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061010 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (Chemotactic Factors) RN - 0 (Transforming Growth Factor beta) SB - IM MH - Cell Communication MH - *Cell Movement MH - Cells, Cultured MH - Chemokine CCL2/*physiology MH - Chemotactic Factors MH - Endothelium, Vascular/cytology MH - Humans MH - Mesenchymal Stem Cells/cytology MH - Muscle, Smooth, Vascular/*cytology MH - *Neovascularization, Physiologic/drug effects MH - Transforming Growth Factor beta/*pharmacology EDAT- 2006/10/13 09:00 MHDA- 2007/03/07 09:00 CRDT- 2006/10/13 09:00 PHST- 2006/10/13 09:00 [pubmed] PHST- 2007/03/07 09:00 [medline] PHST- 2006/10/13 09:00 [entrez] AID - S0006-4971(20)51982-4 [pii] AID - 10.1182/blood-2006-07-036400 [doi] PST - ppublish SO - Blood. 2007 Feb 1;109(3):987-94. doi: 10.1182/blood-2006-07-036400. Epub 2006 Oct 10.