Growth and development alter susceptibility to acute renal injury.
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.
Department of Medicine, University of Washington, Seattle, Washington, USA. dzager@fhcrc.org
Richard A
RA
Zager
Ali C M
AC
Johnson
Masayo
M
Naito
Steve R
SR
Lund
Nayeon
N
Kim
Karol
K
Bomsztyk
D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000367:Age Factors; D000818:Animals; D001835:Body Weight; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D019446:Endotoxemia / Q000150:complications; D005990:Glycerol / Q000633:toxicity; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D008297:Male; D008298:Maleates / Q000633:toxicity; D051379:Mice; D009929:Organ Size; D012319:RNA Polymerase II / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism
D008298:Maleates; D012333:RNA, Messenger; D011973:Receptors, LDL; D051779:Sterol Regulatory Element Binding Proteins; C030272:maleic acid; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D012319:RNA Polymerase II; D005990:Glycerol