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

Thallas-Bonke, Vicki, Coughlan, Melinda T, Tan, Adeline LY, Harcourt, Brooke E, Morgan, Philip E, Davies, Michael J, Bach, Leon A, Cooper, Mark E and Forbes, Josephine M (2013) Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content.. Nephrology (Carlton, Vic.), 18 1: 47-56. doi:10.1111/j.1440-1797.2012.01665.x


Author Thallas-Bonke, Vicki
Coughlan, Melinda T
Tan, Adeline LY
Harcourt, Brooke E
Morgan, Philip E
Davies, Michael J
Bach, Leon A
Cooper, Mark E
Forbes, Josephine M
Title Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content.
Journal name Nephrology (Carlton, Vic.)   Check publisher's open access policy
ISSN 1440-1797
1320-5358
Publication date 2013-01-01
Year available 2012
Sub-type Article (original research)
DOI 10.1111/j.1440-1797.2012.01665.x
Open Access Status Not Open Access
Volume 18
Issue 1
Start page 47
End page 56
Total pages 10
Place of publication Richmond, Australia
Publisher Wiley-Blackwell Publishing Asia
Language eng
Formatted abstract
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.
Keyword Urology & Nephrology
Urology & Nephrology
UROLOGY & NEPHROLOGY
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Mater Research Institute-UQ (MRI-UQ)
 
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Created: Mon, 05 Jan 2015, 21:16:57 EST by Ms Kate Rowe on behalf of Mater Research Institute-UQ