| Targeting the AGE-RAGE axis improves renal function in the context of a healthy diet low in AGE content. | |
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MedLine Citation:
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PMID: 23046363 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-10-10 |
Journal Detail:
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Title: Nephrology (Carlton, Vic.) Volume: - ISSN: 1440-1797 ISO Abbreviation: Nephrology (Carlton) Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9615568 Medline TA: Nephrology (Carlton) Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors Nephrology © 2012 Asian Pacific Society of Nephrology. |
Affiliation:
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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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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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