title: OTUB1 overexpression in mesangial cells is a novel regulator in the pathogenesis of glomerulonephritis through the decrease of DCN level.
abstract: BACKGROUND
  OTUB1 is a member of OTUs (Ovarian-tumor-domain-containing proteases), a deubiquitinating enzymes family (DUBs), which was shown as a proteasome-associated DUB to be involved in the proteins Ub-dependent degradation. It has been reported that OTUB1 was expressed in kidney tissue. But its concrete cellular location and function in the kidney remain unclear. Decorin (DCN) in mesangial cells (MC) is considered to be a potentially important factor for antagonizing glomerulonephritides, and its degradation is mediated by ubiquitination. The aim of this study is to investigate the role of OTUB1 expression in MC and its relationship with DCN during glomerulonephritis.
  
  
  RESULTS
  Using quantitative RT-PCR and Western blot, we demonstrated that OTUB1 mRNA and protein were constitutively expressed in cultured rat MC and found to be upregulated by the stimulation of IL-1β or ATS. OTUB1 overexpression was detected in the mesangial area of glomeruli in some immunocomplex mediated nephritides such as IgA nephropathy, acute diffuse proliferative glomerulonephritis and lupus nephritis by immunohistochemistry. The immunoprecipitation assay demonstrated that OTUB1 interacted with DCN. The overexpression of OTUB1 enhanced the ubiquitination and degradation of DCN in MC.
  
  
  CONCLUSIONS
  These data showed the inflammatory injury could up-regulate OTUB1 expression in MC, which might attribute the promoting effect of OTUB1 on glomerulonephritides to the decrease of DCN level.
authors.affiliation: Key Laboratory of Molecular Medicine of Chinese Education Ministry, Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruimin
authors.initials: R
authors.lastname: Hu
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wu
authors.forename: Weina
authors.initials: W
authors.lastname: Jiang
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Song
authors.forename: Tong
authors.initials: T
authors.lastname: Jin
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Mao
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhao
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D058575:Decorin / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D005921:Glomerulonephritis / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D007518:Isoantibodies / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054875:Ubiquitination; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D058575:Decorin; D053583:Interleukin-1beta; D007518:Isoantibodies; D012333:RNA, Messenger; C035678:anti-Thy antibody; D010450:Endopeptidases; C573232:OTUB1 protein, rat