title: NF-κB upregulates ubiquitin C-terminal hydrolase 1 in diseased podocytes in glomerulonephritis.
abstract: Podocyte injury is a pivotal factor during the progression of glomerular diseases. It has been demonstrated that the expression of ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) is increased in injured podocytes in a number of types of glomerulonephritis. However, its mechanism of regulation remains to be elucidated. A previous study by our group suggested that UCH-L1 is a downstream protein of nuclear factor (NF)-κB signaling. In the present study, the involvement of NF-κB in the regulation of the expression of UCH-L1 was investigated in diseased podocytes in vivo and in vitro. Increases in the expression of phosphorylated NF-κB at p65 and UCH-L1 were detected using immunohistochemical analysis of kidney biopsy tissues from 56 cases of nephritis, including immunoglobulin A nephropathy, membranous glomerulonephritis and lupus nephritis. The two indicators were also analyzed using western blot analysis in cultured murine podocytes stimulated by inflammatory factors. The results of the present study demonstrated that in human renal biopsies of several cases of immune complex-mediated glomerulonephritis, the increases of NF-κB and UCH-L1 were positively correlated with the number of diseased podocytes. By contrast, in non-immune complex-mediated glomerulonephritis, no clear activation of NF-κB and increase of UCH-L1 expression was observed. In vitro, immune stimulation also led to the upregulation of UCH-L1 through the NF-κB signaling pathway in mouse podocytes. In conclusion, the results of the present study suggested that the activation of NF-κB and upregulation of UCH-L1 in podocytes may be vital in podocyte injury associated with immune complex-mediated glomerulonephritis.
authors.affiliation: Department of Pathology, Weifang Medical College, Weifang, Shandong 261053, P.R. China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Xing
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Hu
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Weili
authors.initials: W
authors.lastname: Luo
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D005922:Glomerulonephritis, IGA / Q000378:metabolism / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000201:enzymology* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008181:Lupus Nephritis / Q000378:metabolism / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D050199:Podocytes / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D043222:Ubiquitin Thiolesterase / Q000235:genetics* / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D008840:Microfilament Proteins; D016328:NF-kappa B; C503967:SYNPO protein, human; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C482860:UCHL1 protein, human; D043222:Ubiquitin Thiolesterase