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Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in AGE content.
MedLine Citation:
PMID:  23046363     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
AIM: Mouse chow is commonly high in advanced glycation end products, known contributors to diabetic nephropathy. The aim of this study was to evaluate if targeting of the AGE-RAGE axis was still effective in the context of a diet low in AGE content, which is more comparable to diets consumed by individuals with type 1 diabetes. METHODS: C57BL/6J wild-type (WT) and mice deficient in the receptor for AGEs (RAGE-KO) consumed a diet low in AGE content. Groups of mice were given (i) vehicle (ii) streptozotocin or (iii) streptozotocin + AGE lowering therapy (alagebrium chloride) and followed for 24 weeks. RESULTS: Diabetic mice had high urinary albumin excretion rates, hyperfiltration and release of urinary Kim-1, not seen in diabetic RAGE-KO mice. Diabetic mice also had renal fibrosis, measured by glomerulosclerosis, tubulointerstitial expansion (TIA), TGF-β1 and glomerular collagen-IV deposition which almost all improved by RAGE-KO or alagebium. Diabetic mice had a greater renal burden of AGEs and increased expression of renal specific PKC-α phosphorylation, which was improved in RAGE-KO mice, or those treated with alagebrium. CONCLUSION: Diabetic mice given a low AGE diet still developed renal disease, which could be attenuated by targeting of the AGE-RAGE axis.
Authors:
Vicki Thallas-Bonke; Melinda T Coughlan; Adeline L Y Tan; Brooke E Harcourt; Philip E Morgan; Michael J Davies; Leon A Bach; Mark E Cooper; Josephine M Forbes
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-10
Journal Detail:
Title:  Nephrology (Carlton, Vic.)     Volume:  -     ISSN:  1440-1797     ISO Abbreviation:  Nephrology (Carlton)     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9615568     Medline TA:  Nephrology (Carlton)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Nephrology © 2012 Asian Pacific Society of Nephrology.
Affiliation:
Diabetes Complications Division, Baker IDI Heart & Diabetes Institute, Melbourne, Victoria, Australia; Department of Medicine, Austin and Northern Clinical Schools, University of Melbourne, Victoria, Australia.
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