Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content
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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 Jonathan; Bach, Leon A; Cooper, Mark E; Forbes, Josephine M.
In: Nephrology, Vol. 18, No. 1, 01.2013, p. 47-56.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in advanced glycation end-product content
AU - Thallas-Bonke, Vicki
AU - Coughlan, Melinda T
AU - Tan, Adeline Ly
AU - Harcourt, Brooke E
AU - Morgan, Philip E
AU - Davies, Michael Jonathan
AU - Bach, Leon A
AU - Cooper, Mark E
AU - Forbes, Josephine M
N1 - © 2012 The Authors. Nephrology © 2012 Asian Pacific Society of Nephrology.
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Animals
KW - Diet
KW - Glycosylation End Products, Advanced
KW - Kidney
KW - Male
KW - Mice
KW - Mice, Inbred C57BL
KW - Receptors, Immunologic
U2 - 10.1111/j.1440-1797.2012.01665.x
DO - 10.1111/j.1440-1797.2012.01665.x
M3 - Journal article
C2 - 23046363
VL - 18
SP - 47
EP - 56
JO - Nephrology
JF - Nephrology
SN - 1320-5358
IS - 1
ER -
ID: 128974783