Urotensin II promotes the proliferation of endothelial progenitor cells through p38 and p44/42 MAPK activation.

Urotensin II (UII) is a vasoactive peptide with many potent effects in the cardiorenovascular system and is also possibly involved in the pathogenesis of atherosclerosis. Endothelial progenitor cells (EPCs) are involved in angiogenesis and vascular homeostasis and may be important in the maintenance of endothelial integrity. The aim of this study was to investigate whether UII has an effect on the proliferation of bone marrow-derived EPCs and the possible signaling mechanisms involved. Bone marrow-derived EPCs were isolated from male Sprague-Dawley rats and cultured in medium containing 5% fetal bovine serum. Cells were incubated with UII for 24 h. The proliferation of EPCs was analyzed by MTT assay. Western blotting was performed to determine the phosphorylation levels of mitogen-activated protein kinases (MAPKs). The results demonstrated that UII promoted the proliferation of EPCs in a concentration-dependent manner in a certain range, and the proliferation was largely suppressed by inhibitors of GPR14 and MAPKs (p38 and p44/42). UII significantly increased the phosphorylation levels of p38MAPK and p44/42MAPK, and these effects were significantly inhibited by respective inhibitors. These findings indicate that UII promotes the proliferation of rat bone marrow-derived EPCs through a process that involves MAPK activation, and provides novel insights regarding the role of UII in the EPC-mediated repair of atherosclerotic injury.