[High glucose induces sumoylation of Smad4 via SUMO2/3 in glomerular mesangial cells].

Objective To investigate the expression of SUMO2/3and Smad4in rat glomerular mesangial cells(GMCs)induced by high glucose,and the interaction between small ubiquitin related modifier(SUMO)2/3and Smad4;and to explore the role and mechanism of sumoylation in regulating TGF-βsignaling in diabetic nephropathy.Methods Cultured rat GMCs were divided into five groups:normal glucose group(5.6mmol/L glucose),high glucose groups(10,20and 30 mmol/L glucose),and mannitol group(osmotic control).The expression of SUMO2/3,Smad4and fibronectin(FN)was measured by Western blot and RT-PCR.The interaction and colocalization between SUMO2/3and Smad4were detected by Co-immunoprecipitation and immunofluorescence confocal laser microscopy.Results Compared with controls,the expressions of SUMO2/3,Smad4and FN in the cells in the high glucose groups increased(P0.05).The co-immunoprecipitation and immunofluorescence confocal laser scanning showed that Smad4interacted and colocalized with SUMO2/3and the sumolyation(SUMO2/3)of Smad4was enhanced significantly in the high glucose groups compared with the control group(P0.05).Conclusion Sumolyation of Samd4by SUMO2/3may be involved in the regulation of TGF-βsignaling in diabetic nephropathy.