Urotensin II induces migration of endothelial progenitor cells via activation of the RhoA/Rho kinase pathway.
Urotensin II (UII) is a vasoactive peptide with many potent effects in the cardiorenovascular system and may be involved in the pathogenesis of atherosclerosis. Cardiovascular risk factors are often accompanied by reduced numbers of endothelial progenitor cells (EPCs) and their impaired migratory capacity. However, the role of UII in the migration of EPCs has not been reported so far. The aim of this study was to investigate whether UII influences the chemotactic function of bone marrow-derived EPCs and the possible signaling mechanisms involved. As a ligand for the orphan G-protein coupled receptor 14 (GPR14, UT receptor), UII exerts vasoactive functions through activation of the RhoA/Rho kinase pathway. We therefore analyzed the expression of GPR14 mRNA and protein, the activation of RhoA kinase and the phosphorylation of myosin light chain (MLC) in EPCs, isolated from the rat bone marrow. EPCs of 1-4 passages expressed GPR14 mRNA and protein. Chemotaxis assays were performed using Transwell cell-culture chambers with UII (10(-10)-10(-6) M), showing that UII induced chemotaxis of EPCs in a concentration-dependent manner after 3-h treatment (all p < 0.05), with the highest value (about 3-fold increase) at 10(-8) M. UII caused rapid activation of RhoA and increased phosphorylation of MLC. Conversely, a Rho-kinase inhibitor Y-27632 prevented the UII-induced migration and the phosphorylation of MLC. In conclusion, GPR14/UT receptor is expressed in EPCs, and UII induces migration of EPCs via activation of the RhoA/Rho kinase pathway. These findings provide new insights into the actions of UII in atherosclerosis.
Xu
Shengkai
S
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China.
Jiang
Hong
H
Wu
Bing
B
Yang
Jian
J
Chen
Sisi
S
D000818:Animals; D002465:Cell Movement / Q000187:drug effects*; D002630:Chemotactic Factors / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology* / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D014579:Urotensins / Q000494:pharmacology*; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D002630:Chemotactic Factors; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein