Balance of S1P1 and S1P2 signaling regulates peripheral microvascular permeability in rat cremaster muscle vasculature
Balance of S1P1 and S1P2 signaling regulates peripheral microvascular permeability in rat cremaster muscle vasculature
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DOI：
10.1152/ajpheart.00097.2008
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发表时间：
2009-01-01
影响因子：
4.8
通讯作者：
Lee, Menq-Jer
中科院分区：
文献类型：
--
作者：
Lee, Jen-Fu;Gordon, Sharon;Lee, Menq-Jer
李金峰，Gordon S, Estrada R, Wang L, Siow DL, Wattenberg BW, Lominadze D, Lee MJ。S1P(1)和S1P(2)信号的平衡调节大鼠肌外周微血管通透性。[J] .中国生物医学工程学报，2009,31(6):563 - 567。首次发表于2008年11月14日；doi: 10.1152 / ajpheart.00097.2008。-鞘氨醇-1-磷酸（S1P）调节培养内皮细胞中的各种分子和细胞事件，如细胞骨架重组、细胞-细胞外基质相互作用和细胞间连接相互作用。我们采用Sprague-Dawley大鼠胸肌血管床静脉渗漏模型，探讨S1P信号在微血管通透性调控中的作用。S1P信号是由S1P家族G蛋白偶联受体（S1P（1-5）受体）介导的。S1P(1)和S1P(2)受体分别转导刺激和抑制信号，在肌肌血管内皮中表达。经颈动脉单独给药S1P不能防止组胺诱导的大鼠颈肌血管床静脉渗漏。然而，两种S1P(1)的激动剂SEW2871和FTY720激活S1P(1)介导的信号传导，可显著抑制组胺诱导的微血管渗漏。用VPC 23019处理以拮抗S1P(1)调节的信号，极大地增强了组胺诱导的静脉渗漏。S1P(2)的特异性拮抗剂JTE-013抑制S1P(2)信号后，S1P能够在体内保护微血管通透性。此外，在培养的内皮细胞中，内皮紧密连接和屏障功能受到S1P(1)-和S1P(2)-介导的信号一致调节。这些数据表明，S1P(1)和S1P(2)信号之间的平衡调节了外周循环微血管通透性的稳态，从而可能影响外周血管总阻力。
Lee JF, Gordon S, Estrada R, Wang L, Siow DL, Wattenberg BW, Lominadze D, Lee MJ. Balance of S1P(1) and S1P(2) signaling regulates peripheral microvascular permeability in rat cremaster muscle vasculature. Am J Physiol Heart Circ Physiol 296: H33-H42, 2009. First published November 14, 2008; doi: 10.1152/ajpheart.00097.2008. - Sphingosine-1-phosphate (S1P) regulates various molecular and cellular events in cultured endothelial cells, such as cytoskeletal restructuring, cell-extracellular matrix interactions, and intercellular junction interactions. We utilized the venular leakage model of the cremaster muscle vascular bed in Sprague-Dawley rats to investigate the role of S1P signaling in regulation of microvascular permeability. S1P signaling is mediated by the S1P family of G protein-coupled receptors (S1P(1-5) receptors). S1P(1) and S1P(2) receptors, which transduce stimulatory and inhibitory signaling, respectively, are expressed in the endothelium of the cremaster muscle vasculature. S1P administration alone via the carotid artery was unable to protect against histamine-induced venular leakage of the cremaster muscle vascular bed in Sprague-Dawley rats. However, activation of S1P(1)-mediated signaling by SEW2871 and FTY720, two agonists of S1P(1), significantly inhibited histamine-induced microvascular leakage. Treatment with VPC 23019 to antagonize S1P(1)-regulated signaling greatly potentiated histamine-induced venular leakage. After inhibition of S1P(2) signaling by JTE-013, a specific antagonist of S1P(2), S1P was able to protect microvascular permeability in vivo. Moreover, endothelial tight junctions and barrier function were regulated by S1P(1)- and S1P(2)- mediated signaling in a concerted manner in cultured endothelial cells. These data suggest that the balance between S1P(1) and S1P(2) signaling regulates the homeostasis of microvascular permeability in the peripheral circulation and, thus, may affect total peripheral vascular resistance.