Intervention with tranilast attenuates renal pathology and albuminuria in advanced experimental diabetic nephropathy
| Autor: | Carol A. Pollock, Sally Mifsud, Yuan Zhang, Richard E. Gilbert, Darren J. Kelly, Weier Qi, Jennifer L. Wilkinson-Berka |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Collagen Type IV
medicine.medical_specialty Time Factors Proline Physiology Tranilast Blotting Western Urology Kidney Tritium Nephropathy Diabetes Mellitus Experimental Diabetic nephropathy Animals Genetically Modified Rats Sprague-Dawley Mice Random Allocation Transforming Growth Factor beta Physiology (medical) Internal medicine Diabetes mellitus Renin medicine Albuminuria Animals Humans Diabetic Nephropathies ortho-Aminobenzoates Cells Cultured business.industry Anti-Inflammatory Agents Non-Steroidal Kidney metabolism General Medicine Fibroblasts medicine.disease Fibrosis Immunohistochemistry Fibronectins Rats Endocrinology Renal pathology Nephrology Female medicine.symptom Atrophy business medicine.drug Kidney disease |
| Zdroj: | Nephron. Physiology. 95(4) |
| ISSN: | 1660-2137 |
| Popis: | Background/Aims: Tubulointerstitial pathology with the accumulation of extracellular matrix are pathological hallmarks of diabetic nephropathy that are directly related to declining renal function. Tranilast (N-[3,4-dimethoxycinnamoyl]anthranilic acid), an inhibitor of transforming growth factor-β (TGF-β), used to treat hypertrophic scars has recently been shown in pilot studies to exert a beneficial effect in advanced diabetic nephropathy in humans. However, its effects on diabetic renal pathology are unknown. Methods: Studies were conducted using a transgenic model, the diabetic (mRen-2)27 rat, which develops many of the structural and functional characteristics of human diabetic nephropathy when diabetes is induced with streptozotocin (STZ). An experimental design was chosen to mimic, in part, the clinical context with drug therapy (tranilast 400 mg/kg/ day) initiated in established disease (8 weeks after STZ) and in the presence of persistent hyperglycaemia and hypertension. Results: At 16 weeks, diabetes was associated with progressive albuminuria, tubulointerstitial fibrosis and tubular atrophy. Without affecting blood pressure or blood glucose, tranilast treatment was associated with a 83% reduction in tubulointerstitial fibrosis (p < 0.001), a 58% reduction in tubular atrophy (p < 0.01) and near normalization of albuminuria (p < 0.05) in diabetic Ren-2 rats. In vitro studies in primary cultures of human renal cortical fibroblasts demonstrated a reduction in TGF-β-induced hydroxyproline incorporation and fibronectin synthesis with tranilast 100 µM. Conclusion: Tranilast, when administered during the course of experimental diabetic nephropathy, attenuates tubulointerstitial pathology and albuminuria. These findings are consistent with the antagonist effects of tranilast on TGF-β actions in the diabetic kidney. |
| Databáze: | OpenAIRE |
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