title: Inflammatory factor-specific sumoylation regulates NF-κB signalling in glomerular cells from diabetic rats.
abstract: 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.
authors.affiliation: Department of Geriatric Disease, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China, cnsysy@sina.com.
authors.forename: Sijiao
authors.initials: S
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.forename: Furong
authors.initials: F
authors.lastname: Liu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Li
authors.forename: Yinghua
authors.initials: Y
authors.lastname: Guo
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yang
authors.forename: Jinchun
authors.initials: J
authors.lastname: Xu
authors.forename: Jindan
authors.initials: J
authors.lastname: Song
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism; D006025:Glycosaminoglycans / Q000627:therapeutic use; D020672:I-kappa B Proteins / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*; D058207:Sumoylation; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D006025:Glycosaminoglycans; D020672:I-kappa B Proteins; D007376:Interleukin-2; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; C000591382:SUMO4 protein, rat; D025841:Small Ubiquitin-Related Modifier Proteins; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C007858:glucuronyl glucosamine glycan sulfate