Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP).
Monocyte chemotactic protein-1 (MCP-1) has been recognized as an angiogenic chemokine. The molecular mechanism of MCP-1-mediated angiogenesis remains unknown. We recently identified a novel transcription factor, designated MCP-1-induced protein (MCPIP), in human monocytes after treatment with MCP-1. We investigated whether MCP-1-induced angiogenesis is mediated via MCPIP. Treatment of human umbilical vein endothelial cells (HUVECs) with MCP-1 induced expression of MCPIP and capillary-like tube formation. Knockdown of MCPIP by small interfering RNA (siRNA) suppressed MCP-1-induced angiogenesis-related gene VEGF and HIF-1alpha expression as well as tube formation. Transfection of HUVECs with an MCPIP expression vector induced angiogenesis-related genes and tube formation. Chromatin immunoprecipitation analysis revealed that cadherin (cdh) 12 and cdh19 are in vivo targets of MCPIP. Transfection of HUVECs with MCPIP expression vector activated the expression of cdh12 and cdh19 genes. Knockdown of cdh12 or cdh19 expression markedly inhibited MCPIP-induced capillary-like tube formation. Moreover, knockdown of MCPIP also significantly suppressed MCP-1-induced cdh12 and cdh19 gene expression. Our data strongly suggest that MCP-1-induced angiogenesis is mediated via MCPIP, at least in part through transcriptional activation of cdh12 and cdh19.
Niu
Jianli
J
Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USA.
Azfer
Asim
A
Zhelyabovska
Olga
O
Fatma
Sumbul
S
Kolattukudy
Pappachan E
PE
D015820:Cadherins / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D018919:Neovascularization, Physiologic; D034741:RNA, Small Interfering / Q000235:genetics; D012260:Ribonucleases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
D015820:Cadherins; D018932:Chemokine CCL2; D034741:RNA, Small Interfering; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human