title: High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells.
abstract: The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6mmol/L), high glucose groups (10, 20, and 30mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p<0.05). However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p<0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which could be mostly reversed by adding MG132 (p<0.05). The present results support the hypothesis that high glucose may activate NF-κB inflammatory signaling through IκBα sumoylation and ubiquitination.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan 646000, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Ling
authors.initials: L
authors.lastname: Xu
authors.forename: Xueqin
authors.initials: X
authors.lastname: Zhou
authors.forename: Chenlin
authors.initials: C
authors.lastname: Gao
authors.forename: Maojun
authors.initials: M
authors.lastname: Yang
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.forename: Lan
authors.initials: L
authors.lastname: Jiang
authors.forename: Huakui
authors.initials: H
authors.lastname: Gan
authors.forename: Fang
authors.initials: F
authors.lastname: Gou
authors.forename: Hong
authors.initials: H
authors.lastname: Feng
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003928:Diabetic Nephropathies / Q000209:etiology; D005947:Glucose / Q000008:administration & dosage* / Q000494:pharmacology; D020672:I-kappa B Proteins / Q000378:metabolism*; D050527:Mesangial Cells / Q000378:metabolism*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D051381:Rats; D025842:SUMO-1 Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058207:Sumoylation / Q000187:drug effects; D051996:Transcription Factor RelA / Q000096:biosynthesis
chemical_list: D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D025842:SUMO-1 Protein; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D005947:Glucose
keywords: Diabetic nephropathy; Inflammation; Nuclear factor κB; Sumoylation