1-磷酸鞘氨醇可通过S1PR1 / S1PR3 / PI3K / Akt途径促进内皮祖细胞的增殖并减弱其凋亡。,Cell Biology International

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1-磷酸鞘氨醇可通过S1PR1 / S1PR3 / PI3K / Akt途径促进内皮祖细胞的增殖并减弱其凋亡。
Cell Biology International ( IF 3.3 ) Pub Date : 2018-05-24 , DOI: 10.1002/cbin.10991
Hang Wang _{1,

2} , Hao Huang ₃ , Shi-Fang Ding ₁

Affiliation

鞘氨醇-1-磷酸酯（S1P）是一种具有生物活性的溶血磷脂，参与许多病理生理过程。内皮祖细胞（EPC）在内皮修复和肿瘤血管生成中起着至关重要的作用。研究的目的是确定S1P对EPC增殖和抗凋亡及其信号通路的影响。在这项研究中，我们表明S1P，SEW2871（选择性S1P受体1（S1PR1）激动剂）或CYM5541（选择性S1P受体3（S1PR3）变构激动剂）可促进骨髓（BM）衍生的EPC增殖并减弱其凋亡。此外，研究表明，S1P可以促进EPC的增殖，而用CAY10444（一种S1PR3拮抗剂），VPC23019（一种选择性的S1PR（1）/ S1PR（3）拮抗剂）或LY294002（一种PI3K抑制剂）预处理可以明显抑制SPC。）。搬过来，我们发现S1P可以在体外显着减弱H2 O2诱导的凋亡和caspase-3的激活，而W146（一种S1PR1拮抗剂），VPC23019或LY294002可以显着增加caspase-3的激活并随后增加凋亡。我们的结果表明，S1P的保护作用是通过激活PI3K / Akt途径介导的。此外，观察到S1P促进EPCs增殖主要是通过S1PR3介导的，而H2O2诱导的EPCs凋亡的减弱主要是通过S1PR1介导的。这两种作用都是通过激活PI3K / Akt途径介导的，该途径为冠心病，糖尿病和癌症治疗提供了潜在有用的治疗靶标。而W146（一种S1PR1拮抗剂），VPC23019或LY294002可以显着增加caspase-3的激活并增强凋亡。我们的结果表明，S1P的保护作用是通过激活PI3K / Akt途径介导的。此外，观察到S1P促进EPCs增殖主要是通过S1PR3介导的，而H2O2诱导的EPCs凋亡的减弱主要是通过S1PR1介导的。这两种作用都是通过激活PI3K / Akt途径介导的，该途径为冠心病，糖尿病和癌症治疗提供了潜在有用的治疗靶标。而W146（一种S1PR1拮抗剂），VPC23019或LY294002可以显着增加caspase-3的激活并增强凋亡。我们的结果表明，S1P的保护作用是通过激活PI3K / Akt途径介导的。此外，观察到S1P促进EPCs增殖主要是通过S1PR3介导的，而H2O2诱导的EPCs凋亡的减弱主要是通过S1PR1介导的。这两种作用都是通过激活PI3K / Akt途径介导的，该途径为冠心病，糖尿病和癌症治疗提供了潜在有用的治疗靶标。我们的结果表明，S1P的保护作用是通过激活PI3K / Akt途径介导的。此外，观察到S1P促进EPCs增殖主要是通过S1PR3介导的，而H2O2诱导的EPCs凋亡的减弱主要是通过S1PR1介导的。这两种作用都是通过激活PI3K / Akt途径介导的，该途径为冠心病，糖尿病和癌症治疗提供了潜在有用的治疗靶标。我们的结果表明，S1P的保护作用是通过激活PI3K / Akt途径介导的。此外，观察到S1P促进EPCs增殖主要是通过S1PR3介导的，而H2O2诱导的EPCs凋亡的减弱主要是通过S1PR1介导的。这两种作用都是通过激活PI3K / Akt途径介导的，该途径为冠心病，糖尿病和癌症治疗提供了潜在有用的治疗靶标。

"点击查看英文标题和摘要"

Sphingosine-1-phosphate promotes the proliferation and attenuates apoptosis of Endothelial progenitor cells via S1PR1/S1PR3/PI3K/Akt pathway.

Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that involves in numerous pathophysiological processes. Endothelial progenitor cells (EPCs) play a crucial role in endothelial repair and tumor angiogenesis. The aim of study was to determine the effects of S1P on proliferation and anti-apoptosis of EPCs and their signaling pathways. In this study, we showed that S1P, SEW2871 (a selective S1P receptor 1 (S1PR1) agonist), or CYM5541 (a selective S1P receptor 3 (S1PR3) allosteric agonist promotes the proliferation and attenuates apoptosis of bone marrow (BM)-derived EPCs. Futhermore, it was showed that S1P could promote EPCs proliferation, which could be significantly inhibited by pretreatment with CAY10444 (an S1PR3 antagonist), VPC23019 (a selective S1PR(1)/S1PR(3) antagonist), or LY294002 (a PI3K inhibitor). Moveover, we discovered that S1P could significantly attenuate H2 O2 -induced apoptosis and activation of caspase-3 in vitro, while W146 (an S1PR1 antagonist), VPC23019, or LY294002 could significantly increase the activation of caspase-3 and subsequent augmented apoptosis. Our results indicated that the protective effect of S1P is mediated by activating the PI3K/Akt pathway. In addition, S1P promotion of EPCs proliferation was observed to be mainly mediated through S1PR3 and attenuation of EPCs apoptosis induced by H2 O2 was mainly mediated through S1PR1; both of these effects are mediated by activating the PI3K/Akt pathway, which provides potentially useful therapeutic targets for coronary artery disease, diabetes mellitus, and cancer treatment.

更新日期：2019-11-01

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