Inflammatory factor-specific sumoylation regulates NF-κB signalling in glomerular cells from diabetic rats

The activation of nuclear factor (NF)-κB by cytokines under hyperglycaemic conditions is a potential mechanism for complications in diabetes. We investigated whether small ubiquitin-like modifier 4 (SUMO4) regulates renal NF-κB signalling in diabetic rats.

Histological changes in kidney were analysed in diabetic GK rats. The expressions of tumour necrosis factor (TNF)-α, NF-κB (p65), IκBα and SUMO4 in renal tissues were examined by immunohistochemistry and Western blotting. Primary cultured glomerular endothelial cells from rats were stimulated by TNF-α or interleukin (IL)-2.

The renal expression of TNF-α, NF-κB (p65), IκBα and SUMO4 was significantly higher in diabetic GK rats than in control rats. In control rats, no nuclear translocation was observed for IκBα or NF-κB (p65). However, in diabetic GK rats, translocation of NF-κB (p65) and IκBα into the nucleus was observed, and the expression of SUMO4 and IκBα was up-regulated in the glomerular endothelial cells. SUMO4 was localised in both the cytoplasm and nucleus, while IκBα was predominantly located in the nucleus after stimulation with TNF-α. In contrast, SUMO4 was localised in the nucleus, and increased cytoplasm SUMO4 localisation was found after stimulation with IL-2.

SUMO4 plays a role in regulating NF-κB signalling in glomerular cells. Cytokines have a unique effect in regulating the sumoylation of NF-κB.