All-Trans Retinoic Acid Has a Potential Therapeutic Role for Diabetic Nephropathy.
10.3349/ymj.2015.56.6.1597
- Author:
Chul Sik KIM
1
;
Jong Suk PARK
;
Chul Woo AHN
;
Kyung Rae KIM
Author Information
1. Department of Internal Medicine, Hallym University College of Medicine, Anyang, Korea. ironeat@hallym.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
All-trans retinoic acid;
diabetic nephropathy;
transforming growth factor-beta1;
protein kinase-C;
reactive oxygen species
- MeSH:
Animals;
Diabetes Mellitus, Type 2/*complications;
Diabetic Nephropathies/*complications/*drug therapy/pathology;
Mesangial Cells/*metabolism;
Oxidative Stress/drug effects;
Rats;
Rats, Inbred OLETF;
Reactive Oxygen Species/metabolism;
Transforming Growth Factor beta1/analysis/pharmacology;
Tretinoin/*pharmacology/therapeutic use
- From:Yonsei Medical Journal
2015;56(6):1597-1603
- CountryRepublic of Korea
- Language:English
-
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-beta1 (TGF-beta1), 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-beta1 levels and ROS. Moreover, ATRA treatment showed a dose-dependent decrease in PKC expression. CONCLUSION: ATRA treatment suppressed UAE and TGF-beta1 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.
