LXRs激动剂T0901317通过PI3K/Akt增强人脐静脉内皮细胞的增殖能力

Liver X receptors agonist T0901317 promotes human umbilical vein endothelial cell proliferation via activation of PI3K/Akt pathway

目的观察肝X受体(liver X receptors,LXRs)激动剂T0901317对人脐静脉内皮细胞(human umbilical veinendothelial cell,HUVEC)增殖活性的影响。方法体外分离和培养原代HUVEC,不同浓度的T0901317(0、0.5、2、5μmol/L)干预HUVEC 48 h后,采用MTS法检测HUVEC增殖情况;Western blot检测磷酸化Akt(Ser473)及总Akt的表达。结果T0901317(0～5μmol/L)呈浓度依赖性的促进HUVEC的增殖(P<0.01)和上调HUVEC中p-Akt-Ser473的表达(P<0.01),PI3K抑制剂LY294002(10μmol/L)和基因转录抑制剂放线菌素-D(actinomycin D,Act-D,5μg/ml)可以阻断T0901317(5μmol/L)上调p-Akt-Ser473的作用(P<0.01),提示T0901317通过基因转录调节的方式激活PI3K/Akt信号,此外,PI3K抑制剂LY294002(10μmol/L)预处理可以逆转T0901317(5μmol/L)促HUVEC增殖作用(P<0.01)。结论 LXRs激动剂T0901317可通过激活PI3K/Akt信号通路增强HUVEC的增殖能力。

Objective To observe the effect of liver X receptors（LXRs） agonist T0901317 on human umbilical vein endothelial cells（HUVECs） proliferation.Methods The HUVECs isolated and cultured in vitro were treated with different concentrations of T0901317（0,0.5,2 and 5 μmol/L） for 48 h.The proliferation of HUVECs was evaluated by MTS assay.The expressions of phospho-Akt（Ser473） and total Akt were detected by Western blotting.Results The HUVEC proliferation was significantly promoted and the phospho-Akt（Ser473） expression was significantly upregulated by T0901317 in a dose-dependent manner（P0.01）.The upregulation of phospho-Akt（Ser473） induced by T0901317 could be blocked by PI3K inhibitor LY294002（10 μmol/L） and gene transcription inhibitor actinomycin D（Act-D）（5 μg/ml）（P0.01）,indicating T0901317 activated PI3K/Akt pathway through regulating gene transcription.Moreover,pretreatment of HUVECs with LY294002（10 μmol/L） could reverse T0901317-induced HUVEC proliferation（P0.01）.Conclusion The LXRs agonist T0901317 can promote HUVEC proliferation through the activation of PI3K/Akt pathway.