摘要
目的:探讨微小RNA-451(miR-451)对高糖培养的小鼠肾小球系膜细胞(mesangial cells,MCs)炎症发生的抑制作用及靶向β型蛋白酶体亚基8(proteasome subunitβtype 8,Psmb8)基因的调控机制。方法:分别将MCs培养于低糖和高糖DMEM培养基中,q PCR检测miR-451的表达水平;q PCR检测过表达miR-451后炎症相关因子IL-18和TNF-α的m RNA表达水平;Western blot检测IL-18、TNF-α及Psmb8的蛋白表达水平;Western blot检测低表达Psmb8的MCs中IL-18和TNF-α蛋白的相对表达水平。结果:高糖组MCs的miR-451表达水平较低糖组明显降低(P<0.01),而Psmb8表达却显著增高(P<0.01)。进一步在高糖组过表达miR-451后,Psmb8的表达水平明显降低(P<0.01),炎症相关因子IL-18和TNF-α表达水平亦明显降低(P<0.01)。同时,在高糖组中沉默Psmb8后,IL-18和TNF-α表达水平降低(P<0.01)。结论:miR-451在高糖培养的小鼠肾小球系膜细胞中靶向抑制Psmb8的表达,降低炎症相关因子IL-18和TNF-α蛋白的表达,从而缓解高糖诱导的肾小球系膜细胞的炎症反应。
AIM:To investigate the effect of microRNA(miR)-451by targeting proteasome subunitβtype8(Psmb8)on the inflammatory responses in mouse glomerular mesangial cells(MCs)under high-and low-glucose conditions.METHODS:The expression levels of miR-451,IL-18mRNA and TNF-αmRNA were detected by qPCR.The protein expression levels of IL-18,TNF-αand Psmb8were determined by Western blot when miR-451was over-expressed and down-expressed in the MCs.Moreover,the expression of IL-18and TNF-αwas detected when Psmb8was silenced by si-Psmb8in MCs.RESULTS:The expression of miR-451was significantly decreased in the MCs treated with high glucose compared with low glucose group(P<0.01).However,the expression of Psmb8was increased in high glucose group as compared with low glucose group(P<0.01).Moreover,the expression levels of Psmb8,IL-18and TNF-αwere significantly decreased when miR-451was over-expressed in high glucose group(P<0.01).Additionally,the expression levels of IL-18and TNF-αwere significantly reduced when Psmb8was silenced in the MCs under high glucose condition.CONCLUSION:miR-451reduces the expression of inflammatory factors via targeting Psmb8in the MCs under high glucose condition.Therefore,miR-451may play a role in inflammation of diabetic nephropathy.
作者
姜文豪
孙艳
彭睿
彭惠民
张政
JIANG Wen-hao;SUN Yan;PENG Rui;PENG Hui-min;ZHANG Zheng(College of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016, China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2018年第3期494-499,共6页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81570747)
