Title
Mcp-1-Induced Protein Promotes Endothelial-Like And Angiogenic Properties In Human Bone Marrow Monocytic Cells
Abstract
Monocytic cells enhance neovascularization by releasing proangiogenic mediators and/or by transdifferentiating into endothelial-like cells. However, the mechanisms that govern this transdifferentiation process are largely unknown. Recently, monocyte chemotactic protein-1 (MCP-1)-induced protein (MCPIP) has been identified as a novel CCCH-type zinc-finger protein expressed primarily in monocytic cells. Here, we analyzed whether MCPIP might exert angiogenic effects by promoting differentiation of monocytic cells into endothelial cell (EC)-like phenotype. The expression of MCPIP increased during MCP-1-induced transdifferentiation in human bone marrow mononuclear cells (BMNCs). Knockdown of MCPIP with small interfering RNA (siRNA) abolished MCP-1-induced expression of EC markers Flk-1 and Tie-2 in human BMNCs. BMNCs transfected with MCPIP expression vector displayed EC-like morphology accompanied by downregulation of monocytic markers CD14 and CD11b, upregulation of EC markers Flk-1 and Tie-2, induction of cadherin (cdh)-12 and -19, activation of endoplasmic reticulum (ER) stress, and autophagy. Knockdown of cdh-12 or cdh-19 markedly inhibited MCPIP-induced enhancement of cell attachment and EC-marker expression. Inhibition of ER stress by tauroursodeoxycholate abolished MCPIP-induced expression of EC markers. Inhibition of autophagy by knockdown of Beclin-1 with siRNA or by an autophagy inhibitor 3′-methyladenine inhibited MCPIP-induced expression of EC markers. Expression of MCPIP in BMNCs enhanced uptake of acetylated low-density lipoprotein (acLDL), formation of EC-colony, incorporation of cells into capillary-like structure on Matrigel, and exhibited increased neovascularization in the ischemic hindlimb in mice. These results demonstrate that MCPIP may be an important regulator of inflammatory angiogenesis and provide novel mechanistic insights into the link between MCP-1 and cardiovascular diseases. Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics.
Publication Date
11-1-2013
Publication Title
Journal of Pharmacology and Experimental Therapeutics
Volume
347
Issue
2
Number of Pages
288-297
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1124/jpet.113.207316
Copyright Status
Unknown
Socpus ID
84886079953 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/84886079953
STARS Citation
Niu, Jianli; Wang, Kangkai; Zhelyabovska, Olga; Saad, Yasser; and Kolattukudy, Pappachan E., "Mcp-1-Induced Protein Promotes Endothelial-Like And Angiogenic Properties In Human Bone Marrow Monocytic Cells" (2013). Scopus Export 2010-2014. 6428.
https://stars.library.ucf.edu/scopus2010/6428