Abstract
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-1α 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
.