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Growth and development alter susceptibility to acute renal injury.

Zager, Richard A and Johnson, Ali C M and Naito, Masayo and Lund, Steve R and Kim, Nayeon and Bomsztyk, Karol (2008) Growth and development alter susceptibility to acute renal injury. Kidney international, 74 (5). pp. 674-678. ISSN 1523-1755

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Many of the studies of acute renal injury have been conducted in young mice usually during their rapid growth phase; yet, the impact of age or growth stage on the degree of injury is unknown. To address this issue, we studied three forms of injury (endotoxemic-, glycerol-, and maleate-induced) in mice ranging in age from adolescence (3 weeks) to maturity (16 weeks). The severity of injury within each model significantly correlated with weight and age. We also noticed a progressive age-dependent reduction in renal cholesterol content, a potential injury modifier. As the animals grew and aged they also exhibited stepwise decrements in the mRNAs of HMG CoA reductase and the low density lipoprotein receptor, two key cholesterol homeostatic genes. This was paralleled by decreased amounts of RNA polymerase II and the transcription factor SREBP1/2 at the reductase and lipoprotein receptor gene loci as measured by chromatin immunoprecipitation. Our study shows that the early phase of mouse growth can profoundly alter renal susceptibility to diverse forms of experimental acute renal injury.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URL above.
DOI: 10.1038/ki.2008.251
PubMed ID: 18563055
PMCID: PMC2744310
Grant Numbers: R01 DK068520-05, R01 GM045134-16, R37 DK045978-15
Keywords or MeSH Headings: Age Factors; Animals; Body Weight; Cholesterol/blood/metabolism; Endotoxemia/complications; Glycerol/toxicity; Hydroxymethylglutaryl CoA Reductases/genetics; Kidney/drug effects/growth & development/metabolism/pathology; Kidney Failure, Acute/etiology/genetics/metabolism/pathology; Male; Maleates/toxicity; Mice; Organ Size; RNA Polymerase II/metabolism; RNA, Messenger/genetics/metabolism; Receptors, LDL/genetics; Sterol Regulatory Element Binding Proteins/metabolism;
Subjects: Cellular and Organismal Processes > Aging
Cellular and Organismal Processes > Development
Depositing User: Library Staff
Date Deposited: 14 Jul 2009 21:41
Last Modified: 14 Feb 2012 14:42

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