SUMO E3 Ligase PIASy Mediates High Glucose-Induced Activation of NF-κB Inflammatory Signaling in Rat Mesangial Cells

• Published in: Mediators of Inflammation Vol. 2017; no. 2017; pp. 1 - 9
• Main Authors: Xu, Yong, Long, Yang, Jiang, Chunxia, Gao, Chenlin, Zhou, Luping, Dong, Jianhua, Liang, Yaling, Huang, Wei, Chen, Meijuan
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Limiteds 01.01.2017; Hindawi Publishing Corporation; Hindawi; Hindawi Limited
• Subjects: Cell cycle; Cytokines; Deoxyribonucleic acid; Diabetes mellitus; DNA; Enzyme-linked immunosorbent assay; Enzymes; Genotoxicity; Glucose; IKK protein; Inflammation; Interleukin 6; Isoforms; Kinases; Medical research; Mesangial cells; Monocyte chemoattractant protein 1; Nephropathy; NF-κB protein; Oxidative stress; Phosphorylation; Proteins; siRNA; SUMO protein; Therapeutic applications; Transcription factors; Trends; Ubiquitin-protein ligase; China
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2017/1685194

Background. Sumoylation is extensively involved in the regulation of NF-κB signaling. PIASy, as a SUMO E3 ligase, has been proved to mediate sumoylation of IκB kinase γ (IKKγ) and contribute to the activation of NF-κB under genotoxic agent stimulation. However, the association of PIASy and NF-κB signaling in the pathogenesis of diabetic nephropathy (DN) has not been defined. Methods. Rat glomerular mesangial cells (GMCs) were stimulated by high glucose; siRNA was constructed to silence the expression of PIASy; the expression of PIASy, SUMO isoforms (SUMO1, SUMO2/3), and NF-κB signaling components was analyzed by Western blot; the interaction between IKKγ and SUMO proteins was detected by coimmunoprecipitation; and the release of inflammatory cytokines MCP-1 and IL-6 was assayed by ELISA. Results. High glucose significantly upregulated the expression of PIASy, SUMO1, and SUMO2/3 in a dose- and time-dependent manner (P<0.05), induced the phosphorylation and sumoylation of IKKγ (P<0.05), and then triggered NF-κB signaling whereas MCP-1 and IL-6 were released from GMCs (P<0.05). Moreover, these high glucose-induced effects were observably reversed by siRNA-mediated knockdown of PIASy (P<0.05). Conclusion. The SUMO E3 ligase PIASy mediates high glucose-induced activation of NF-κB inflammatory signaling, suggesting that PIASy may be a potential therapeutic target of DN.