Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content

Vicki Thallas-Bonke, Melinda T Coughlan, Adeline Tan, Brooke Elise Harcourt, Philip E Morgan, Michael Jonathan Davies, Leon Ashley Bach, Mark Cooper, Josephine M Forbes

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)

Abstract

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. C57BL/6J wild-type 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. 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, TGF-?1 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-a phosphorylation, which was improved in RAGE-KO mice, or those treated with alagebrium. Diabetic mice given a low-AGE diet still developed renal disease, which could be attenuated by targeting of the AGE-RAGE axis.
Original languageEnglish
Pages (from-to)47 - 56
Number of pages10
JournalNephrology
Volume18
Issue number1
DOIs
Publication statusPublished - 2013

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