Urotensin II promotes the proliferation of endothelial progenitor cells through p38 and p44/42 MAPK activation
Urotensin II promotes the proliferation of endothelial progenitor cells through p38 and p44/42 MAPK activation
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尾加压素 II 通过 p38 和 p44/42 MAPK 激活促进内皮祖细胞增殖
DOI：
10.3892/mmr.2012.899
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发表时间：
2012-07-01
影响因子：
3.4
通讯作者：
Jiang, Hong
中科院分区：
文献类型：
--
作者：
Xu, Shengkai;Wen, Huazhi;Jiang, Hong
尿紧张素II （UII）是一种血管活性肽，在心血管系统中具有许多有效作用，也可能参与动脉粥样硬化的发病机制。内皮祖细胞（EPCs）参与血管生成和血管稳态，并可能在维持内皮完整性方面发挥重要作用。本研究的目的是探讨UII是否对骨髓源性EPCs的增殖有影响及其可能的信号机制。从雄性Sprague-Dawley大鼠中分离出骨髓来源的EPCs，并在含有5%胎牛血清的培养基中培养。用UII孵育细胞24 h， MTT法检测EPCs的增殖情况。Western blotting检测丝裂原活化蛋白激酶（MAPKs）的磷酸化水平。结果表明，UII在一定范围内以浓度依赖的方式促进EPCs的增殖，而GPR14和MAPKs抑制剂（p38和p44/42）的增殖在很大程度上受到抑制。UII显著增加了p38MAPK和p44/42MAPK的磷酸化水平，这些作用被各自的抑制剂显著抑制。这些发现表明，UII通过一个涉及MAPK激活的过程促进大鼠骨髓源性EPCs的增殖，并提供了关于UII在EPCs介导的动脉粥样硬化损伤修复中的作用的新见解。
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 angio-genesis 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.