International journal of molecular sciences, 2019-09, Vol.20 (18), p.4393
2019
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- Autor(en) / Beteiligte
- Titel
- Targeting ROS and cPLA2/COX2 Expressions Ameliorated Renal Damage in Obese Mice with Endotoxemia
- Ist Teil von
- International journal of molecular sciences, 2019-09, Vol.20 (18), p.4393
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Obesity is associated with metabolic endotoxemia, reactive oxygen species (ROS), chronic inflammation, and obese kidney fibrosis. Although the fat-intestine-kidney axis has been documented, the pathomechanism and therapeutic targets of obese kidney fibrosis remain unelucidated. To mimic obese humans with metabolic endotoxemia, high-fat-diet-fed mice (HF group) were injected with lipopolysaccharide (LPS) to yield the obese kidney fibrosis-metabolic endotoxemia mouse model (HL group). Therapeutic effects of ROS, cytosolic phospholipases A2 (cPLA2) and cyclooxygenase-2 (COX-2) inhibitors were analyzed with a quantitative comparison of immunohistochemistry stains and morphometric approach in the tubulointerstitium of different groups. Compared with basal and HF groups, the HL group exhibited the most prominent obese kidney fibrosis, tubular epithelial lipid vacuoles, and lymphocyte infiltration in the tubulointerstitium. Furthermore, inhibitors of nonspecific ROS, cPLA2 and COX-2 ameliorated the above renal damages. Notably, the ROS-inhibitor-treated group ameliorated not only oxidative injury but also the expression of cPLA2 and COX-2, indicating that ROS functions as the upstream signaling molecule in the inflammatory cascade of obese kidney fibrosis. ROS acts as a key messenger in the signaling transduction of obese kidney fibrosis, activating downstream cPLA2 and COX-2. The given antioxidant treatment ameliorates obese kidney fibrosis resulting from a combined high-fat diet and LPS-ROS could serve as a potential therapeutic target of obese kidney fibrosis with metabolic endotoxemia.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms20184393Titel-ID: cdi_doaj_primary_oai_doaj_org_article_74f5924979464df897c0ce55078002b8
- Format
- –
- Schlagworte
- Adipose tissue, Animals, Aristolochic acid, Biomarkers, Cell injury, cPLA2 and COX-2, Cyclooxygenase 2 - genetics, Cyclooxygenase 2 - metabolism, Cyclooxygenase-2, Diabetes, Disease Models, Animal, Endotoxemia, Endotoxemia - complications, Epithelial Cells - drug effects, Epithelial Cells - metabolism, Epithelium, Fibrosis, Forkhead protein, FOXO1 protein, Gene expression, Gene Expression Regulation - drug effects, Immunohistochemistry, Inflammation, Kidney diseases, Kidney Diseases - drug therapy, Kidney Diseases - etiology, Kidney Diseases - metabolism, Kidney Diseases - pathology, Lipid Metabolism, Lipids, Lymphocytes, Lymphocytes - immunology, Lymphocytes - metabolism, Macrophages, Metabolic disorders, Metabolic syndrome, Mice, Microbiota, Molecular Targeted Therapy, NAD(P)H oxidase, Nitrotyrosine, NOX4 protein, obese kidney fibrosis, Obesity, Obesity - complications, Oxidative Stress, Phospholipases A2, Cytosolic - genetics, Phospholipases A2, Cytosolic - metabolism, Proteins, Reactive Oxygen Species - metabolism, ROS, Signal transduction, Signal Transduction - drug effects, Stains & staining, Therapeutic applications, Vacuoles