All-Trans Retinoic Acid Has a Potential Therapeutic Role for Diabetic Nephropathy

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MeSH: Animals ; Diabetes Mellitus, Type 2/complications* ; Diabetic Nephropathies/complications* ; Diabetic Nephropathies/drug therapy* ; Diabetic Nephropathies/pathology ; Mesangial Cells/metabolism* ; Oxidative Stress/drug effects ; Rats ; Rats, Inbred OLETF ; Reactive Oxygen Species/metabolism ; Transforming Growth Factor beta1/analysis ; Transforming Growth Factor beta1/pharmacology ; Tretinoin/pharmacology* ; Tretinoin/therapeutic use

Keywords: All-trans retinoic acid ; diabetic nephropathy ; protein kinase-C ; reactive oxygen species ; transforming growth factor-β₁

Abstract: PURPOSE: The aim of this study was to examine the effects of all-trans retinoic acid (ATRA) on diabetic nephropathy.
MATERIALS AND METHODS: We measured amounts of urinary albumin excretion (UAE) after administrating ATRA to Otsuka Long-Evans Tokushima Fatty (OLETF) rats. In order to understand the mechanism of action for ATRA, we administrated ATRA to examine its inhibitory action on the production of transforming growth factor-β₁ (TGF-β₁), protein kinase C (PKC), and reactive oxidative stress (ROS) in cultured rat mesangial cells (RMCs).
RESULTS: After 16 weeks of treatment, UAE was lower in the ATRA-treated OLETF rats than in the non-treated OLETF rats (0.07±0.03 mg/mgCr vs. 0.17±0.15 mg/mgCr, p<0.01). After incubation of RMCs in media containing 30 or 5 mM of glucose, treatment with ATRA showed time- and dose-dependent decreases in TGF-β₁ levels and ROS. Moreover, ATRA treatment showed a dose-dependent decrease in PKC expression.
CONCLUSION: ATRA treatment suppressed UAE and TGF-β₁ synthesis, which was mediated by significant reductions in PKC activity and ROS production. Our results suggest that ATRA has a potential therapeutic role for diabetic nephropathy.