斯钙素2在高糖诱导的肝细胞炎症反应中的作用机制

The mechanism of Stanniocalcin 2 in high glucose-induced liver cells inflammatory effect

目的研究斯钙素2(STC2)在糖尿病肝病中的作用机制。方法分析GEO数据库,筛选与糖尿病肝病模型相关的新颖分子。分析链脲佐菌素(STZ)诱导的糖尿病模型小鼠肝脏的STC2的表达水平。高糖诱导处理LO2肝细胞,检测STC2表达变化,并分析TNF-α和IL-6的变化,评价STC2与TNF-α和IL-6的表达相关性。构建稳定高表达STC2的LO2细胞株,qRT-PCR分析高糖处理下过表达细胞与对照细胞中TNF-α和IL-6的表达。Western Blot分析STC2过表达细胞与对照细胞的STAT3和NF-κB的激活水平;MTT实验检测过表达STC2的LO2细胞的增殖能力。结果高脂饮食和STZ诱导糖尿病模型小鼠的肝组织STC2表达水平显著增加。在LO2肝细胞中,高糖能够诱导STC2的表达,并诱导炎症因子TNF-α和IL-6的表达,STC2与TNF-α和IL-6的表达存在正相关的关系。过表达STC2能够激活STAT3和NF-κB通路,并抑制肝细胞的增殖。结论在高糖环境下肝细胞的STC2被诱导表达,并且与促炎性因子TNF-α和IL-6存在正相关的关系。过表达STC2还能够激活STAT3和NF-κB通路,并抑制肝细胞的增殖。

Objective To study the mechanism of stanniocalcin 2(STC2) in diabetic liver disease.Methods Underlying analysis of GEO database,a novel gene associated with diabetic disease model was screened.The expression of STC2 in the liver tissue from streptozotocin(STZ)-induced diabetic mice was analyzed.The expression of STC2 and inflammatory factors were measured in high glucose treated LO2 cells,and the correlation between STC2 and TNF-α or IL-6 were analyzed.Then stable high expressing STC2 was constructed in LO2 cells,RT-PCR was subjected to explore the effect of STC2 in the inflammatory process by high glucose.The activation of STAT3 and NF-κB were measured by western blotting.MTT assay was subjected to evaluate the proliferation when overexpressed with STC2.Results The expression of STC2 in liver was highly increased in the HFD and STZ-induced diabetic mice.When exposed to high glucose in LO2 cells,the STC2 expression was significantly enhanced.And the pro-inflammatory factors were augmented by high glucose treatment,and the expression of STC2 was positively correlated with inflammatory factors.Furthermore,overexpression of STC2 could activate STAT3 and NF-κB pathways and inhibited the proliferation of liver cells.Conclusions The expression of STC2 is induced by high glucose and is positively correlated with pro-inflammatory factors in the high glucose.Importantly,overexpression of STC2 can enhance the activation of STAT3 and NF-κB pathways and inhibit the proliferation of liver cells.