title: All-Trans Retinoic Acid Has a Potential Therapeutic Role for Diabetic Nephropathy.
abstract: OBJECTIVE
  The aim of this study was to examine the effects of all-trans retinoic acid (ATRA) on diabetic nephropathy.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine, Hallym University College of Medicine, Anyang, Korea. ironeat@hallym.ac.kr.
authors.forename: Chul Sik
authors.initials: CS
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea. acw@yuhs.ac.
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Ahn
authors.affiliation: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyung Rae
authors.initials: KR
authors.lastname: Kim
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D050527:Mesangial Cells / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D020334:Rats, Inbred OLETF; D017382:Reactive Oxygen Species / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D014212:Tretinoin
keywords: All-trans retinoic acid; diabetic nephropathy; protein kinase-C; reactive oxygen species; transforming growth factor-β₁