title: Usp2-69 overexpression slows down the progression of rat anti-Thy1.1 nephritis.
abstract: Mesangial proliferative glomerulonephritis is characterized by proliferation of mesangial cells (MCs) and transforming growth factor-β (TGF-β)-dependent stimulation of abnormal extracellular matrix (ECM) accumulation. We previously showed that Decorin--a leucine-rich proteoglycan inhibiting the progression of glomerulonephritis and glomerular sclerosis--can be degraded by the ubiquitin-proteasome pathway and deubiquitinated and stabilized by ubiquitin-specific processing protease 2-69(Usp2-69). Usp2-69 is highly expressed in the kidney and has been implicated in the regulation of cell proliferation and apoptosis. However, its role in mesangial proliferative glomerulonephritis remains unclear. Here, we explored the effect of Usp2-69 on MC proliferation and ECM deposition by transfecting Usp2-69 plasmid into rat anti-Thy1.1 nephritis model and into cultured MCs, as well as detected Usp2-69 and Decorin in rat anti-Thy1.1 nephritis model by western blot. Overexpressing Usp2-69 at the early stage, but not advanced stage, of anti-Thy1.1 nephritis alleviated cell proliferation and ECM deposition, which was shown by decreased Ki-67, Collagen IV and Fibronectin detected by immunohistochemistry. Overexpression also increased Decorin and decreased TGF-β1 and Collagen IV both in vitro and in vivo. In conclusion, our findings suggest that Usp2-69 overexpression alleviates the progression of rat anti-Thy1.1 nephritis and, therefore, that exogenous plasmid injection via the renal artery enhanced by electrotransfer technology could be a promising avenue for glomerular disease research.
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China; Key Laboratory of Molecular Medicine, Chinese Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Xing
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Weili
authors.initials: W
authors.lastname: Luo
authors.affiliation: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, PR China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Nianji
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Linda Wei
authors.initials: LW
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China; Shanghai Institute for Kidneys and Dialysis, Shanghai, PR China; Key Laboratory of Molecular Medicine, Chinese Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, PR China. Electronic address: zzg@shmu.edu.cn.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Shanghai Medical College, Fudan University, Shanghai, PR China; Shanghai Institute for Kidneys and Dialysis, Shanghai, PR China; Key Laboratory of Molecular Medicine, Chinese Ministry of Education, Shanghai Medical College, Fudan University, Shanghai, PR China. Electronic address: hjwu@shmu.edu.cn.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Wu
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D024141:Collagen Type IV / Q000378:metabolism; D058575:Decorin / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000378:metabolism*; D009393:Nephritis / Q000378:metabolism* / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
chemical_list: D024141:Collagen Type IV; D058575:Decorin; D007518:Isoantibodies; D009124:Muscle Proteins; D053773:Transforming Growth Factor beta1; C035678:anti-Thy antibody; D043222:Ubiquitin Thiolesterase; C464656:Usp2 protein, rat
keywords: Decorin; Extracellular matrix; Gene therapy; Mesangial cell; Ubiquitin-specific processing protease 2; anti-Thy1.1 nephritis