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: Hongxia Zhang, Xing Mao, Yu Sun, Ruimin Hu, Weili Luo, Zhonghua Zhao, Qi Chen, Zhigang Zhang
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 12 Issue 2 Pg. 2893-901 (Aug 2015) ISSN: 1791-3004 [Electronic] Greece
• PMID: 25976522 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-1beta
• Lipopolysaccharides
• Microfilament Proteins
• NF-kappa B
• SYNPO protein, human
• Transcription Factor RelA
• Tumor Necrosis Factor-alpha
• UCHL1 protein, human
• Ubiquitin Thiolesterase

Topics

• Animals
• Cells, Cultured
• Coculture Techniques
• Glomerulonephritis, IGA (metabolism, pathology)
• Glomerulonephritis, Membranous (enzymology, metabolism, physiopathology)
• Humans
• Immunohistochemistry
• Interleukin-1beta (pharmacology)
• Kidney (metabolism, pathology)
• Lipopolysaccharides (toxicity)
• Lupus Nephritis (metabolism, pathology)
• Male
• Microfilament Proteins (genetics, metabolism)
• NF-kappa B (metabolism)
• Phosphorylation (drug effects)
• Podocytes (cytology, metabolism)
• Rats
• Rats, Sprague-Dawley
• Real-Time Polymerase Chain Reaction
• Transcription Factor RelA (metabolism)
• Tumor Necrosis Factor-alpha (pharmacology)
• Ubiquitin Thiolesterase (genetics, metabolism)
• Up-Regulation (drug effects)