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.
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, Florida (J N., O.Z., Y.S., P.E.K.); Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, People's Republic of China (K.W.).
authors.forename: Jianli
authors.initials: J
authors.lastname: Niu
authors.forename: Kangkai
authors.initials: K
authors.lastname: Wang
authors.forename: Olga
authors.initials: O
authors.lastname: Zhelyabovska
authors.forename: Yasser
authors.initials: Y
authors.lastname: Saad
authors.forename: Pappachan E
authors.initials: PE
authors.lastname: Kolattukudy
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018929:Cell Culture Techniques; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000502:physiology*; D017690:Cell Transplantation; D003094:Collagen; D016207:Cytokines / Q000276:immunology; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D006801:Humans; D007511:Ischemia / Q000628:therapy; D007797:Laminin; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D018919:Neovascularization, Physiologic / Q000276:immunology; D011509:Proteoglycans; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012260:Ribonucleases; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D034741:RNA, Small Interfering; D014157:Transcription Factors; C059485:matrigel; D003094:Collagen; D012260:Ribonucleases; C510646:ZC3H12A protein, human