Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone Prevents Albuminuria but Not Glomerulosclerosis in Experimental Diabetes
العنوان: | Peroxisome Proliferator-Activated Receptor-γ Agonist Rosiglitazone Prevents Albuminuria but Not Glomerulosclerosis in Experimental Diabetes |
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المؤلفون: | Giancarlo Viberti, Anthea Hayward, G Setti, Rudolf W. Bilous, Kathryn White, Cecile Dessapt, Francesca Barone, R Buckingham, Gabriella Gruden, Luigi Gnudi, Kawachi Hiroshi |
المصدر: | American Journal of Nephrology. 32:393-402 |
بيانات النشر: | S. Karger AG, 2010. |
سنة النشر: | 2010 |
مصطلحات موضوعية: | Male, Agonist, medicine.medical_specialty, endocrine system diseases, medicine.drug_class, Peroxisome proliferator-activated receptor, Kidney, urologic and male genital diseases, Diabetes Mellitus, Experimental, Rats, Sprague-Dawley, Rosiglitazone, Nephrin, Diabetic nephropathy, Downregulation and upregulation, Internal medicine, Albuminuria, Animals, Hypoglycemic Agents, Medicine, Diabetic Nephropathies, Cells, Cultured, Chemokine CCL2, chemistry.chemical_classification, biology, urogenital system, business.industry, Macrophages, Membrane Proteins, Glomerulosclerosis, medicine.disease, female genital diseases and pregnancy complications, Rats, PPAR gamma, Endocrinology, chemistry, Nephrology, biology.protein, Thiazolidinediones, medicine.symptom, business, medicine.drug |
الوصف: | Backgrounds/Aims:Renal inflammation and nephrin downregulation contribute to albuminuria in diabetes. We studied, in streptozotocin-induced diabetic rats, the effect of rosiglitazone (RSG), a peroxisome proliferator-activated receptor-γ agonist, on renal macrophage infiltration, MCP1, and nephrin expression in relation to albuminuria. Methods: We investigated control and diabetic rats treated or untreated with RSG. Animals were sacrificed at 1, 3, and 9 months. Renal MCP1 and nephrin expression were studied by immunoblotting, renal macrophage infiltration by immunohistochemistry, and albuminuria by ELISA. Electron microscopy was used to assess glomerular ultrastructural morphology. In vitroexperiments were conducted in isolated cultured rat glomeruli. Results: Glycaemic control was similar in diabetic rats treated and untreated with RSG, and blood pressure was comparable in all groups. RSG prevented diabetes-induced albuminuria at 9 months, and renal macrophage infiltration and MCP1 upregulation at 3 and 9 months. Diabetes-mediated nephrin downregulation was abolished by RSG. Diabetes-induced glomerulosclerosis, glomerular basement membrane thickening, and foot process fusion were not affected by RSG. In isolated glomeruli, MCP1 directly induced nephrin downregulation and this was prevented by RSG. RSG had no effect on nephrin expression. Conclusion: RSG prevents albuminuria and nephrin downregulation in experimental diabetes independently of glycaemic and blood pressure control. This effect likely occurs via correction of diabetes-induced inflammatory processes. |
تدمد: | 1421-9670 0250-8095 |
الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c4b7e1785f198e4288b5fa686920a542Test https://doi.org/10.1159/000320129Test |
حقوق: | CLOSED |
رقم الانضمام: | edsair.doi.dedup.....c4b7e1785f198e4288b5fa686920a542 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14219670 02508095 |
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