KLF4在内毒素血症小鼠中的表达模式及其意义

Expression Patterns and Potential Role of KLF4 in Mouse Endotoxemia Induced by Lipopolysaccharide

目的探讨Kruppel样因子4(Kruppel-like factor 4,KLF4)在内毒素血症小鼠中的表达模式及意义。方法运用实时荧光PCR技术和Western blot技术,分别从mRNA水平和蛋白水平探讨内毒素血症小鼠肝脏和肺脏中KLF4的表达;运用生物信息学技术,对启动子区含有KLF4的结合位点的炎症介质基因进行了预测;运用RT-PCR技术,从mRNA水平探讨内毒素血症小鼠肝脏和肺脏中IL-1β的表达模式。结果内毒素血症小鼠肝脏和肺脏中KLF4 mRNA的表达下调,KLF4蛋白的表达先下调后升高;IL-1β、IL-15I、L-12、IL-18、IL-10等炎症介质基因的启动子区均含有KLF4的结合元件,这些炎症基因的表达可能直接受到KLF4的调控;内毒素血症小鼠肝脏和肺脏中IL-1β的表达模式与KLF4的表达模式呈相反趋势。结论内毒素血症小鼠肝脏和肺脏中KLF4表达下调,KLF4在炎症介质基因表达调控中可能具有重要作用。

Objective This study was designed to explore the expression patterns of KLF4 and its possible role in mouse endotoxemia. Methods Real-time PCR was used to detect the KLF4 mRNA in the liver and lungs and Western-blotting was performed to detect the KLF4 protein expression. Bioinformatics technology was used to analyze the specific DNA sequence in promotors of inflammatory mediators to which KLF4 may bind. RT-PCR was used to explore the expression patterns of IL-1β gene in mouse endotoxemia induced by LPS. Results The results showed that 1） the expression of KLF4 mRNA was down-regulated in the liver and lungs in the endotoxemic mice while KLF4 protein was down-regulated followed by up-regulation; 2） several inflammatory mediator genes such as IL-1β, IL-15, IL-12, IL-18 and IL-10 contain KLF4 binding sequences in their promotors, indicating that they may be regulated directly by KLF4; 3） the expression patterns of KLF4 and IL-1β gene induced by LPS were opposite. Conclusion This study for the first time has revealed the expression patterns of KLF4 during endotoxemia in mouse, and found that KLF4 might play important role in the expression regulation of inflammatory mediator genes during endotoxemia.