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Growth and development alter susceptibility to acute renal injury

Richard A Zager1, Ali C M Johnson, Masayo Naito

  • 1Department of Medicine, University of Washington, Seattle, Washington, USA. dzager@fhcrc.org

Kidney International
|June 20, 2008
PubMed

Insights

Age significantly impacts acute renal injury severity in mice. Kidney injury susceptibility decreases with age due to reduced cholesterol and altered gene expression during growth.

Area of Science:

  • Nephrology
  • Developmental Biology
  • Biochemistry

Background:

  • Acute renal injury research often uses young, rapidly growing mice, but the influence of age on injury severity is unclear.
  • Understanding age-related susceptibility is crucial for interpreting experimental acute renal injury models.
  • Cholesterol metabolism plays a role in kidney function and may be affected by age.

Purpose of the Study:

  • To investigate the effect of age and growth stage on the severity of acute renal injury in mice.
  • To explore the relationship between age, renal cholesterol content, and gene expression related to cholesterol homeostasis.
  • To determine if developmental stage influences susceptibility to different types of experimental kidney injury.

Main Methods:

  • Induction of acute renal injury using three models: endotoxemic, glycerol, and maleate.
  • Assessment of injury severity in mice across a range of ages (3 to 16 weeks).
  • Measurement of renal cholesterol content, mRNA levels of key cholesterol genes (HMG CoA reductase, LDL receptor), and associated transcription factors (SREBP1/2) via chromatin immunoprecipitation.

Main Results:

  • Injury severity in all models significantly correlated with mouse age and weight.
  • A progressive, age-dependent decrease in renal cholesterol content was observed.
  • Stepwise decrements in the mRNA of cholesterol homeostatic genes and related transcription factors were noted with increasing age.

Conclusions:

  • The early growth phase in mice significantly alters renal susceptibility to various experimental acute renal injuries.
  • Age-related changes in renal cholesterol content and gene expression are associated with altered injury severity.
  • Findings highlight the importance of considering developmental stage in acute renal injury research.

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