Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content
Research output: Contribution to journal › Journal article › Research › peer-review
Vicki Thallas-Bonke, Melinda T Coughlan, Adeline Ly Tan, Brooke E Harcourt, Philip E Morgan, Michael Jonathan Davies, Leon A Bach, Mark E Cooper, Josephine M Forbes
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 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, 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.
|Number of pages||10|
|Publication status||Published - Jan 2013|
- Animals, Diet, Glycosylation End Products, Advanced, Kidney, Male, Mice, Mice, Inbred C57BL, Receptors, Immunologic