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

• Published in: Inflammation research Vol. 63; no. 1; pp. 23 - 31
• Main Authors: Chen, Sijiao, Yang, Tao, Liu, Furong, Li, Hongyan, Guo, Yinghua, Yang, Hongyan, Xu, Jinchun, Song, Jindan, Zhu, Zhiming, Liu, Daoyan
• Format: Journal Article
• Language: English
• Published: Basel Springer Basel 2014
• Subjects: Allergology; Animals; Anti-Inflammatory Agents - therapeutic use; Biomedical and Life Sciences; Biomedicine; Cells, Cultured; Dermatology; Diabetes Mellitus - drug therapy; Diabetes Mellitus - metabolism; Diabetes Mellitus - pathology; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - metabolism; Diabetic Nephropathies - pathology; Endothelial Cells - metabolism; Glycosaminoglycans - therapeutic use; I-kappa B Proteins - metabolism; Immunology; Interleukin-2 - metabolism; Kidney Glomerulus - metabolism; Kidney Glomerulus - pathology; Kidney Glomerulus - ultrastructure; Male; Neurology; NF-kappa B - metabolism; NF-KappaB Inhibitor alpha; Original Research Paper; Pharmacology/Toxicology; Rats; Rats, Wistar; Rheumatology; Signal Transduction; Small Ubiquitin-Related Modifier Proteins - metabolism; Sumoylation; Tumor Necrosis Factor-alpha - metabolism; NF-kappa-B; Diabetic microvascular lesion; Diabetic nephropathy; Cytokines; Small ubiquitin-like modifier
• ISSN: 1023-3830; 1420-908X
• DOI: 10.1007/s00011-013-0675-3

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