Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing
Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing
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DOI：
10.1152/ajpcell.2000.278.3.c612
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发表时间：
2000-03-01
影响因子：
5.5
通讯作者：
An, SZ
中科院分区：
文献类型：
--
作者：
Lee, H;Goetzl, EJ;An, SZ
溶血磷脂酸(LPA)和1-磷酸鞘氨醇(S1P)是一种强有力的脂类生长因子，具有相似的刺激细胞骨架功能的能力。它们的作用是由内皮分化基因(EDGs)编码的G蛋白偶联受体(GPCRs)亚家族介导的。我们推测，活化的血小板产生大量的LPA和S1P可能会影响内皮细胞的功能。通过体外伤口愈合实验，我们观察到LPA和S1P可促进表达LPA受体Edg2和S1P受体Edg1和Edg3的人脐静脉内皮细胞和成年牛主动脉内皮细胞损伤单层的关闭。伤口愈合的两个主要组成部分，细胞迁移和增殖，分别被两种脂类刺激。LPA和S1P还可促进细胞内钙动员和丝裂原活化蛋白激酶(MAPK)的磷酸化。百日咳毒素部分阻断了这两种脂类对内皮细胞迁移、MAPK磷酸化和钙动员的影响，暗示内皮细胞内G(I/O)偶联受体信号转导。LPA和S1P在Ca~(2+)反应中不相互交叉脱敏，提示不同的受体参与其中。因此，LPA和S1P通过不同的GPCRs激活的信号通路影响内皮细胞的功能，并可能有助于损伤血管的愈合。
Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are potent lipid growth factors with similar abilities to stimulate cytoskeleton-based cellular functions. Their effects are mediated by a subfamily of G protein-coupled receptors (GPCRs) encoded by endothelial differentiation genes (edgs). We hypothesize that large quantities of LPA and S1P generated by activated platelets may influence endothelial cell functions. Using an in vitro wound healing assay, we observed that LPA and S1P stimulated closure of wounded monolayers of human umbilical vein endothelial cells and adult bovine aortic endothelial cells, which express LPA receptor Edg2, and S1P receptors Edg1 and Edg3. The two major components of wound healing, cell migration and proliferation, were stimulated individually by both lipids. LPA and S1P also stimulated intracellular Ca2+ mobilization and mitogen-activated protein kinase (MAPK) phosphorylation. Pertussis toxin partially blocked the effects of both lipids on endothelial cell migration, MAPK phosphorylation, and Ca2+ mobilization, implicating G(i/o)-coupled receptor signaling in endothelial cells. LPA and S1P did not cross-desensitize each other in Ca2+ responses, suggesting involvement of distinct receptors. Thus LPA and S1P affect endothelial cell functions through signaling pathways activated by distinct GPCRs and may contribute to the healing of wounded vasculatures.