Beyond proteinuria: VDR activation reduces renal inflammation in experimental diabetic nephropathy
| Autor: | Milica Bozic, Petya Valcheva, Alberto Ortiz, Mercè Ibarz, Elizabeth Córdoba-Lanús, Olga Gracia, Elvira Fernández, Jose M. Valdivielso, Juan F. Navarro-González, M. D. Sanchez-Nino |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Paricalcitol medicine.medical_specialty Calcitriol Physiology Kidney urologic and male genital diseases Calcitriol receptor Diabetes Mellitus Experimental Rats Sprague-Dawley Diabetic nephropathy Mice Internal medicine medicine Albuminuria Animals Diabetic Nephropathies Proteinuria Bone Density Conservation Agents Podocytes business.industry Glomerulonephritis medicine.disease Rats Calcium Channel Agonists Glucose medicine.anatomical_structure Endocrinology Gene Expression Regulation Ergocalciferols Receptors Calcitriol medicine.symptom business medicine.drug |
| Zdroj: | American Journal of Physiology-Renal Physiology. 302:F647-F657 |
| ISSN: | 1522-1466 1931-857X |
| DOI: | 10.1152/ajprenal.00090.2011 |
| Popis: | Local inflammation is thought to contribute to the progression of diabetic nephropathy. The vitamin D receptor (VDR) activator paricalcitol has an antiproteinuric effect in human diabetic nephropathy at high doses. We have explored potential anti-inflammatory effects of VDR activator doses that do not modulate proteinuria in an experimental model of diabetic nephropathy to gain insights into potential benefits of VDR activators in those patients whose proteinuria is not decreased by this therapy. The effect of calcitriol and paricalcitol on renal function, albuminuria, and renal inflammation was explored in a rat experimental model of diabetes induced by streptozotocin. Modulation of the expression of mediators of inflammation by these drugs was explored in cultured podocytes. At the doses used, neither calcitriol nor paricalcitol significantly modified renal function or reduced albuminuria in experimental diabetes. However, both drugs reduced the total kidney mRNA expression of IL-6, monocyte chemoattractant protein (MCP)-1, and IL-18. Immunohistochemistry showed that calcitriol and paricalcitol reduced MCP-1 and IL-6 in podocytes and tubular cells as well as glomerular infiltration by macrophages, glomerular cell NF-κB activation, apoptosis, and extracellular matrix deposition. In cultured podocytes, paricalcitol and calcitriol at concentrations in the physiological and clinically significant range prevented the increase in MCP-1, IL-6, renin, and fibronectin mRNA expression and the secretion of MCP-1 to the culture media induced by high glucose. In conclusion, in experimental diabetic nephropathy VDR activation has local renal anti-inflammatory effects that can be observed even when proteinuria is not decreased. This may be ascribed to decreased inflammatory responses of intrinsic renal cells, including podocytes, to high glucose. |
| Databáze: | OpenAIRE |
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