Effect of NF-κB signal pathway in murine lupus nephritis / 中国免疫学杂志

ABSTRACT

Objective:To investigate the expression and mechanism of NF-κB signal pathway in murine lupus nephritis.Methods:The BXSB mice as well as C57BL/6 of 16 weeks were used.Transmission electron microscope and PAS were used to detect the pathological change of renal tissue.RT-PCR and ELISA were used to detect the expression of HMGB1 mRNA and protein.The expression of HMGB1,p- NF-κB,RAGE,IκB and PCNA protein was detected by immunohistochemical stain,FCM and Western blot.Results:The level of BUN in serum and Micro-albumin in urine of BXSB mice was higher than that in C57BL/6 mice.The expression of HMGB1 mRNA and HMGB1 protein level in peripheral blood increased significantly in BXSB group.Compared with those in control group,electron microscopy and PAS revealed the thickness of glomerular basement membrane(GBM),fusion of foot processes partly of epithelial dell and subepithelial electron-dense deposits in the renal tissue of BXSBA mice.Compared with that of control group,expression of PCNA was higher in glomeruli of BXSB mouse.HMGB1 protein over-expression localized in cytoplasm and extracellular milieu,especially in proliferative glomeruli in BXSB group,while the HMGB1 protein primarily confined to the nuclear of tubule in control group.In BXSB group,the expression of p-NF-κB and RAGE increased,while the expression of IκB decreased.There were positive correlation between the expression of HMGB1,RAGE and p-NF-κB protein (r=0.833,0.621,0.848,P＜0.01),while the expression of p-NF-κB protein negatively correlated with that of IκB.Conclusion:HMGB1 could activate NF-κB through combining with its receptor-RAGE,induce the form of proliferative glomerulonephritis by promoting the proliferation of inherent cell of glomeruli,which may play an important role in the murine lupus nephritis.