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首页> 外文期刊>Journal of Cellular Physiology >PECAM-1 modulates thrombin-induced tissue factor expression on endothelial cells.
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PECAM-1 modulates thrombin-induced tissue factor expression on endothelial cells.

机译：PECAM-1调节thrombin-induced组织因素在内皮细胞表达。

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Platelet endothelial cell adhesion molecule-1 (PECAM-1) (CD31) is known to inhibit platelet function and thrombus formation. The mechanisms involved in PECAM-1's roles as a modulator of hemostasis are still not completely understood. We examined the role of PECAM-1 as a regulator of tissue factor (TF) expression, a known important inducer of thrombosis. Wildtype and CD31KO mice underwent transient (30 min) renal ischemia followed by 24 h re-perfusion and their kidneys assessed for apoptosis, fibrin formation, and tissue factor expression. CD31KO mice exhibited increased tubular epithelial and endothelial apoptosis, increased fibrin deposition, and tissue factor expression. Human umbilical vein endothelial cells (HUVEC) transfected with antisense (AS) PECAM-1 oligonucleotides to downregulate PECAM-1 expression, exhibited greater induction of TF mRNA and protein expression as well as increased expression and nuclear localization of the transcription factor Egr-1 compared to scrambled AS PECAM-1 (Scr)-treated HUVEC following thrombin stimulation. TF induction was found to be mediated through thrombin receptor PAR-1 and the Galphai/o subunit of G-protein, confirmed by PAR-1 antagonist and pertussis toxin inhibition respectively. Thrombin-mediated TF induction was dependent on Rho Kinase activity, phosphorylation of p38(MAPK) and p85 & Akt dephosphorylation. The inverse correlation of PI3K-Akt phosphorylation with p38 (MAPK) phosphorylation was confirmed by pharmacological inhibition. These studies suggest that PECAM-1 is involved in regulating a signaling pathway, affecting PI3K and Akt activation, p38 (MAPK) phosphorylation, which in turn, affects Egr-1 expression and nuclear translocation, ultimately affecting TF expression. These findings provide new insights into the action of PECAM-1 as a modulator of thrombosis.
机译：血小板内皮细胞粘附molecule-1(PECAM-1) (CD31)抑制血小板功能和血栓形成。参与PECAM-1的角色的调制器止血仍然没有被完全了解。我们检查了PECAM-1的调节器的作用组织因子(TF)表达,一个已知的重要血栓形成的诱导物。经历了短暂的肾缺血(30分钟)其次是24小时re-perfusion和肾脏评估细胞凋亡、纤维蛋白形成和组织因子的表达。增加管状上皮和内皮细胞凋亡,增加纤维蛋白沉积组织因子的表达。血管内皮细胞(HUVEC)转染反义(AS) PECAM-1寡核苷酸表达下调PECAM-1表情,展出更大的感应TF信使rna和蛋白质表达以及表达和增加核转录因子的定位相比Egr-1 PECAM-1炒(Scr)治疗HUVEC凝血酶刺激。通过凝血酶受体PAR-1和介导的Galphai / o g蛋白的亚基,证实了PAR-1拮抗剂和百日咳毒素抑制分别。依赖于ρ激酶活性,磷酸化p38 MAPK和p85 & Akt的去磷酸化。PI3K-Akt磷酸化的负相关与p38 MAPK)证实了磷酸化药物抑制。PECAM-1是参与调节信号通路,影响PI3K和Akt激活,p38 MAPK)磷酸化,从而影响Egr-1表达式和核易位,最终影响特遣部队表达式。PECAM-1的调制器的作用血栓形成。

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