CYLD Deubiquitinase Negatively Regulates High Glucose-Induced NF-κB Inflammatory Signaling in Mesangial Cells. (12th November 2017)

• Record Type: Journal Article
• Authors: Li, Yanhui; Huang, Wei; Xu, Youhua; Zhou, Luping; Liang, Yaling; Gao, Chenlin; Long, Yang; Xu, Yong
• Other Names: Collino Massimo Academic Editor.
• Is Part Of: BioMed research international. Volume 2017(2017)
• Publication Date: 2017-11-12
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Life sciences -- Periodicals; 610.5
• DOI: 10.1155/2017/3982906
• Languages: English
• ISSNs: 2314-6133

Abstract

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.