RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation.
RhoA-Rho kinase and platelet-activating factor stimulation of ovine foetal pulmonary vascular smooth muscle cell proliferation.
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DOI：
10.1111/cpr.12052
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发表时间：
2013-10
影响因子：
8.5
通讯作者：
Ibe BO
中科院分区：
文献类型：
--
作者：
Renteria LS;Austin M;Lazaro M;Andrews MA;Lustina J;Raj JU;Ibe BO
血小板激活因子（PAF）由肺血管平滑肌细胞（PVSMC）产生。我们研究了 Rho 激酶对 PAF 刺激 PVSMC 增殖的影响，试图了解 RhoA/Rho 激酶对 PAF 诱导的羊胎儿肺血管重塑的作用。我们的假设是，PAF 作为其下游信号之一，通过 Rho 激酶发挥作用，诱导子宫内胎儿缺氧肺部环境中的动脉 (SMC-PA) 和静脉 (SMC-PV) 生长。通过 DNA 合成、Western 和免疫细胞化学研究了 Rho 激酶和 MAPK 对 PAF 受体 (PAFR) 介导的细胞生长和 PAFR 表达的影响。还研究了构建体 T19N 和 G14V 对 PAF 诱导的细胞增殖的影响。缺氧增加了 PVSMC 增殖，Rho 激酶抑制剂 Y-27632 和 Fasudil (HA-1077) 以及 MAPK 抑制剂 PD 98059 和 SB 203580 减弱了 PAF 对细胞增殖的刺激。 RhoA T19N 和 G14V 刺激细胞增殖，但与 PAF 共孵育并不影响构建体的增殖效果。 Y-27632 和 HA-1077 均显着下调两种细胞类型中的 PAFR 蛋白表达，且具有可比性。此外，用 Y-27632 处理的细胞显示出较少的 PAF 受体荧光，细胞形态显着破坏。我们的结果表明，Rho 激酶通过 PAFR 蛋白的翻译修饰非特异性地调节 PAFR 介导的反应，并表明在体内，PAF 激活 Rho 激酶可能是维持 PAFR 介导的 PVSMC 生长的另一种途径。
Platelet Activating Factor (PAF) is produced by pulmonary vascular smooth muscle Cells (PVSMC). We studied effect of Rho kinase on PAF stimulation of PVSMC proliferation in an attempt to understand a role for RhoA/Rho kinase on PAF-induced ovine fetal pulmonary vascular remodeling. Our hypothesis is that PAF acts through Rho kinase, as one of its downstream signaling, to induce arterial (SMC-PA) and venous (SMC-PV) growth in the hypoxic lung environment of the fetus in utero. Rho kinase and MAPK effects on PAF receptor (PAFR)-mediated cell growth and PAFR expression were studied by DNA synthesis, Western and immunocytochemistry. Effects of constructs T19N and G14V on PAF-induced cell proliferation was also studied. Hypoxia increased PVSMC proliferation and the Rho kinase inhibitors, Y-27632 and Fasudil (HA-1077) as well as MAPK inhibitors PD 98059 and SB 203580 attenuated PAF stimulation of cell proliferation. RhoA T19N and G14V stimulated cell proliferation, but co-incubation with PAF did not affect proliferative effects of the constructs. PAFR protein expression was significantly down-regulated in both cell types by both Y-27632 and HA-1077 with comparable profiles. Also cells treated with Y-27632 showed less PAF receptor fluorescence with significant disruption of the cell morphology. Our results show that Rho kinase nonspecifically modulates PAFR-mediated responses via a translational modification of PAFR protein and suggest that, in vivo, activation of Rho kinase by PAF may be one other pathway to sustain PAFR-mediated PVSMC growth.
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影响因子：
1.7
作者：
Chang, Weiyuan;Chen, Jing;Hoyle, Gary W.
通讯作者：
Hoyle, Gary W.
DOI：
10.1152/ajplung.00420.2003
发表时间：
2004-07-01
影响因子：
4.9
作者：
Martin, C;Göggel, R;Uhlig, S
通讯作者：
Uhlig, S
DOI：
10.1152/ajplung.00042.2008
发表时间：
2008-11-01
影响因子：
4.9
作者：
Badejo, Adeleke M., Jr.;Dhaliwal, Jasdeep S.;Kadowitz, Philip J.
通讯作者：
Kadowitz, Philip J.
影响因子：
24.3
作者：
Dewachter, L.;Adnot, S.;Eddahibi, S.
通讯作者：
Eddahibi, S.
影响因子：
3.8
作者：
Ibe, BO;Portugal, AM;Raj, JU
通讯作者：
Raj, JU