SUMOylation Of NF-κB Signaling Molecules In Rat Mesangial Cells Induced By High Glucose

Objective: Diabetic nephropathy is one of the mostprevalent and serious microvascular complications of diabetes. Post-translational modification of proteins by the small ubiquitin-likemodifiers (SUMO) has emerged as an important regulatory mechanismfor alteration of protein activity, stability, and cellular localization.Thelatest research demonstrated that SUMO were extensively involved inthe regulation of NF-κB pathway,which play critical roles in regulatinginflammation and contribute to diabetic nephropathy.However,the rolesof SUMOylation in regulating NF-κB signaling on the diabeticnephropathy is unclear. This study observed the change of interactionbetween SUMO proteins (SUMO1, SUMO2/3) and NF-κB pathwayrelated signaling molecules (IκBα, IKKγ) in cultured rat GlomerularMesangial Cells(GMCs) stimulated by high glucose. Methods: culturedrat GMCs (HBZY-1) were divided into5groups: normal glucosegroup(5.6mmol/L), high glucose groups(10,20and30mmol/L),Mannitol group was used as osmotic control group,the expression ofSUMO1, SUMO2/3, IκBα, IKKγ, NF-κBp65, MCP-1was measured byWestern blot and RT-PCR, interaction between SUMO1,SUMO2/3andIκBα, IKKγ was observed by co-immunoprecipitation andimmunofluorescence confocus microscope. Result:1, The expression of SUMO1, SUMO2/3was enhanced in high glucose group in a dose andtime-dependent manner(p<0.05).2, In high glucose group,theexpression of IκBα was decreased(p<0.05) but the expression of IKKγwithout change(p>0.05).3, The expression of the SUMOylation(SUMO1,SUMO2/3) of IκBα, IKKγ in high glucose and Mannitol groupwere significantly decreased compared with normal glucosegroup(p<0.05).4, The expression of NF-κBp65, MCP-1was enhanced inhigh glucose group in a dose and time-dependent manner(p<0.05).Conclusion: Our studies suggest that:1, High glucose can increasesignificantly the expression of SUMO1, SUMO2/3, and change theinteraction between SUMO1,SUMO2/3and IκBα, IKKγ;2,High glucosecan degradate IκB-α,but had no obvious effect on expression of IKK γ incultured mesangial cells;3, High glucose may be take part in thepathogenesis of diabetic nephropathy via impacting SUMOylation of IκBspecifically and activation of NF-κB signaling.