All-TransRetinoic Acid Has a Potential Therapeutic Role for Diabetic Nephropathy

Chul Sik Kim, Jong Suk Park, Chul Woo Ahn, Kyung Rae Kim
2015 Yonsei medical journal  
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
more » ... 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 dosedependent 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.
doi:10.3349/ymj.2015.56.6.1597 pmid:26446642 pmcid:PMC4630048 fatcat:rxno65mdw5ernbwn5unh2dkdzi