Title

Monocyte chemotactic protein (MCP)-1 promotes angiogenesis via a novel transcription factor, MCP-1-induced protein (MCPIP)

Authors

Authors

J. Niu; A. Azfer; O. Zhelyabovska; S. Fatma;P. E. Kolattukudy

Comments

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Abbreviated Journal Title

J. Biol. Chem.

Keywords

HUMAN ENDOTHELIAL-CELLS; N-CADHERIN; LUMEN FORMATION; VE-CADHERIN; GROWTH; APOPTOSIS; MCP-1; IDENTIFICATION; MORPHOGENESIS; ACTIVATION; Biochemistry & Molecular Biology

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-1 alpha 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.

Journal Title

Journal of Biological Chemistry

Volume

283

Issue/Number

21

Publication Date

1-1-2008

Document Type

Article

Language

English

First Page

14542

Last Page

14551

WOS Identifier

WOS:000255941400042

ISSN

0021-9258

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