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CYLD Deubiquitinase Negatively Regulates High Glucose-Induced NF- κ B Inflammatory Signaling in Mesangial Cells.
- Source :
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BioMed research international [Biomed Res Int] 2017; Vol. 2017, pp. 3982906. Date of Electronic Publication: 2017 Nov 12. - Publication Year :
- 2017
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Abstract
- Nuclear factor-kappa B (NF- κ B) is the key part of multiple signal transduction of inflammation in the pathogenesis of diabetic nephropathy (DN). The ubiquitin-proteasome system is extensively involved in the regulation of the NF- κ B pathway. Cylindromatosis (CYLD) has deubiquitinase activity and acts as a negative regulator of the NF- κ B signaling pathway. However, the association between CYLD and NF- κ B inflammatory signaling in DN is unclear. In the present study, mouse glomerular mesangial cells (GMCs) and rat GMCs were stimulated by elevated concentrations of glucose (10, 20, and 30 mmol/L high glucose) or mannitol as the osmotic pressure control. CYLD was overexpressed or suppressed by transfection with a CYLD expressing vector or CYLD-specific siRNA, respectively. Our data showed that high glucose significantly inhibited the protein and mRNA expression of CYLD in a dose- and time-dependent manner (both p < 0.05). siRNA-mediated knockdown CYLD facilitated the high glucose-induced activation of NF- κ B signaling and triggered the release of MCP-1, IL-6, and IL-8 (all p < 0.05). However, these high glucose-mediated effects were blunted by overexpression of CYLD ( p < 0.05). The present results support the involvement of CYLD in the regulation of NF- κ B inflammatory signaling induced by elevated glucose, implicating CYLD as a potential therapeutic target of DN.
- Subjects :
- Animals
Chemokine CCL2 genetics
Deubiquitinating Enzyme CYLD
Diabetic Nephropathies pathology
Gene Expression Regulation
Glucose metabolism
Humans
Inflammation pathology
Interleukin-6 genetics
Interleukin-8 genetics
Mesangial Cells pathology
Mice
NF-kappa B genetics
RNA, Small Interfering genetics
Rats
Signal Transduction
Cysteine Endopeptidases genetics
Diabetic Nephropathies genetics
Inflammation genetics
Mesangial Cells metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2314-6141
- Volume :
- 2017
- Database :
- MEDLINE
- Journal :
- BioMed research international
- Publication Type :
- Academic Journal
- Accession number :
- 29259980
- Full Text :
- https://doi.org/10.1155/2017/3982906