High Glucose Induces Sumoylation of Smad4 via SUMO23 in Mesangial Cells

Abstract EN

Recent studies have shown that sumoylation is a posttranslational modification involved in regulation of the transforming growth factor-β (TGF-β) signaling pathway, which plays a critical role in renal fibrosis in diabetic nephropathy (DN).

However, the role of sumoylation in the regulation of TGF-β signaling in DN is still unclear.

In the present study, we investigated the expression of SUMO (SUMO1 and SUMO2/3) and Smad4 and the interaction between SUMO and Smad4 in cultured rat mesangial cells induced by high glucose.

We found that SUMO1 and SUMO2/3 expression was significantly increased in the high glucose groups compared to the normal group P<0.05.

Smad4 and fibronectin (FN) levels were also increased in the high glucose groups in a dose-dependent manner.

Coimmunoprecipitation and confocal laser scanning revealed that Smad4 interacted and colocalized with SUMO2/3, but not with SUMO1 in mesangial cells.

Sumoylation (SUMO2/3) of Smad4 under high glucose condition was strongly enhanced compared to normal control P<0.05.

These results suggest that high glucose may activate TGF-β/Smad signaling through sumoylation of Samd4 by SUMO2/3 in mesangial cells.