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

Authors
 Chul Sik Kim  ;  Jong Suk Park  ;  Chul Woo Ahn  ;  Kyung Rae Kim 
Citation
 YONSEI MEDICAL JOURNAL, Vol.56(6) : 1597-1603, 2015 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
2015
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.
Files in This Item:
T201503958.pdf Download
DOI
10.3349/ymj.2015.56.6.1597
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Rae(김경래)
Park, Jong Suk(박종숙) ORCID logo https://orcid.org/0000-0002-5385-1373
Ahn, Chul Woo(안철우) ORCID logo https://orcid.org/0000-0003-3733-7486
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/141503
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