title: High Glucose and Lipopolysaccharide Activate NOD1- RICK-NF-κB Inflammatory Signaling in Mesangial Cells.
abstract: Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the development and progression of diabetes mellitus (DM) and diabetic nephropathy (DN). The TLR2, TLR4, and NLRP3 inflammasomes of the innate immune system produce various proinflammatory cytokines and are critically involved in inflammatory responses in kidney tissues. The NOD-like receptor (NLR) NOD1 is involved in the NF-κB inflammatory signaling pathway and has an important role in the development of insulin resistance. Extracellular stimuli such as high glucose or lipopolysaccharide (LPS) can induce NOD1-RICK to activate NF-κB, which is associated with diabetes and other chronic inflammatory conditions. It is currently unknown whether NOD1-RICK-mediated NF-κB signaling is involved in DN pathogenesis. In this study, expression of NOD1, RICK, IκBα, NF-κB and IL-1β was detected in cultured rat glomerular mesangial cells (rGMCs) stimulated with high concentrations of glucose and LPS. ML130, a NOD1 inhibitor, was used to investigate the role of the NOD1 signaling pathway in DN inflammation. Our results showed that high glucose or LPS increased the protein and mRNA expression of NOD1, RICK,NF-κBp65 and IL-1β, but attenuated IκBα expression (P<0.05). These changes were synergistically enhanced by stimulating with high glucose and LPS. However, pretreatment with the NOD1 inhibitor ML130 significantly reversed these changes (P<0.05). These combined results support the hypothesis that high glucose and LPS can activate the NOD1-RICK-NF-κB inflammatory signaling pathway via the NOD1 receptor, and may participate in the development of DN.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: F
authors.initials: F
authors.lastname: Gou
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: H
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Endocrinology, the Central Hospital of Guangyuan, Guangyuan, Sichuan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: C
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: G
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou, Sichuan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D005947:Glucose; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D050527:Mesangial Cells / Q000378:metabolism* / Q000473:pathology; D053474:Nod1 Signaling Adaptor Protein / Q000378:metabolism*; D051381:Rats; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D053474:Nod1 Signaling Adaptor Protein; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D005947:Glucose