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NFκB upregulates ubiquitin Cterminal hydrolase 1 in diseased podocytes in glomerulonephritis

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Podocyte injury is a pivotal factor during the progression of glomerular diseases. It has been demonstrated that the expression of ubiquitin carboxyterminal hydrolase L1 (UCHL1) 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 UCHL1 is a downstream protein of nuclear factor (NF)κB signaling. In the present study, the involvement of NFκB in the regulation of the expression of UCHL1 was investigated in diseased podocytes in vivo and in vitro. Increases in the expression of phosphorylated NFκB at p65 and UCHL1 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 complexmediated glomerulonephritis, the increases of NFκB and UCHL1 were positively correlated with the number of diseased podocytes. By contrast, in nonimmune complexmediated glomerulonephritis, no clear activation of NFκB and increase of UCHL1 expression was observed. In vitro, immune stimulation also led to the upregulation of UCHL1 through the NFκB signaling pathway in mouse podocytes. In conclusion, the results of the present study suggested that the activation of NFκB and upregulation of UCHL1 in podocytes may be vital in podocyte injury associated with immune complexmediated glomerulonephritis.
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Document Type: Research Article

Affiliations: 1: Department of Pathology, Weifang Medical College, Weifang, Shandong 261053, P.R. China 2: Department of Pathology and Key Laboratory of Molecular Medicine (Ministry of Education), College of Basic Medicine, Fudan University, Shanghai 200032, P.R. China

Publication date: August 1, 2015

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  • Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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