鸢尾素抑制JAK/STAT3通路促进炎症状态下的血管生成

Irisin promotes angiogenesis in inflammatory state by inhibiting the JAK/STAT3 pathway

目的研究急性炎症状态下鸢尾素对人脐静脉内皮细胞(humanumbilicalveinendothelial cell,HUVEC)血管生成的影响及其机制。方法通过CCK-8检测不同浓度(0.1、1.0、5.0、10.0、20.0ng/mL)的鸢尾素对HUVEC增殖的影响;用脂多糖诱导HUVEC急性炎症状态,通过划痕和成管实验,研究鸢尾素对细胞迁移及管样形成的影响,通过RT-PCR研究相关细胞因子IL-1β、IL-6、TNF-α、PDGF-BB的基因表达;Westernblot检测JAK/STAT3信号通路中关键蛋白Erk1/2、Jak、Stat3的表达。结果各浓度的重组鸢尾素均不影响HUVEC的增殖;在急性炎症状态下,鸢尾素可以促进HUVEC细胞迁移和管样形成,并且抑制HUVEC炎症因子IL-1β、IL-6、TNF-α基因的表达,增加组织修复相关因子PDGF-BB的基因表达;鸢尾素抑制LPS诱导的JAK/STAT3通路激活。结论鸢尾素可以抑制JAK/STAT3信号通路,缓解LPS诱导的HUVEC急性炎症状态,促进血管新生。

Objective To investigate the effect of irisin on angiogenesis in human umbilical vein endothelial cell(HUVEC)under acute inflammatory state and its regulatory mechanism.Methods(1)The effects of different concentrations(0.1,1.0,5.0,10.0,20.0 ng/ml)of irisin on HUVEC proliferation were detected by CCK-8;(2)Acute inflammatory state of HUVEC was induced by LPS.The effect of irisin on cell migration and tubular formation was studied by scratch and tube forming experiments.The gene expression of related cytokines IL-1β,IL-6,TNF-αand PDGF-BB was studied by RT-PCR;(3)The expressions of proteins Erk1/2,Jak and Stat3 in the JAK/STAT3 signaling pathway were detected by Western Blot.Results(1)The change of concentrations of recombinant irisin did not affect the proliferation of HUVEC;(2)Irisin promoted cell migration and tubular formation of HUVEC in the state of acute inflammation,and inhibited the expression of inflammatory factors IL-1β,IL-6 and TNF-αin HUVEC in the state of acute inflammation,and increased the gene expression of tissue repair factor PDGF-BB;(3)Irisin inhibited LPS-induced activation of the JAK/STAT3 pathway.Conclusions Irisin suppresses JAK/STAT3 signaling pathway,relieves acute inflammatory state of HUVEC induced by LPS,and promotes angiogenesis.