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Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Global analysis of gene expression in renal ischemia-reperfusion in the mouse
Takumi Yoshida1, Shiow-Shih Tang, Li-Li Hsiao
1Renal Division, Department of Medicine, Brigham and Women's Hospital, Cambridge, Massachusetts 02139 , USA.
Abstract:
Ischemia-induced acute renal failure (ARF) is a relatively common disorder with major morbidity and mortality. To study global gene expression during ARF, 6-week-old C57BL/6 male mice underwent 30 min of bilateral renal ischemia followed by reperfusion [I/R] or sham operation. Oligonucleotide microarrays [Affymetrix] with approximately 10,000 genes, 6,643 of which were present in mouse kidney, were used to analyze mRNA expression for up to 4 days following I/R. Fifty-two genes at day 1 and 40 at day 4 were up-regulated more than 4-fold [400%]. Seventy genes at day 1 and 30 genes at day 4 were down-regulated to under 0.25-fold from baseline [25%]. Real-time quantitative RT-PCR confirmed changes in expression for 8 genes of interest. Most of the induced transcripts are involved in cell structure, extracellular matrix, intracellular calcium binding, and cell division/differentiation. Our data identified several novel genes that may be important in renal repair after ischemia.
Insights
Acute renal failure (ARF) involves significant gene expression changes. This study identified novel genes involved in kidney repair after ischemia-reperfusion injury in mice.
Area of Science:
- Nephrology
- Molecular Biology
- Genomics
Background:
- Ischemia-induced acute renal failure (ARF) is a common condition with high morbidity and mortality.
- Understanding the molecular mechanisms of ARF is crucial for developing effective treatments.
Purpose of the Study:
- To investigate global gene expression patterns during acute renal failure induced by ischemia-reperfusion (I/R).
- To identify novel genes potentially involved in renal repair following ischemic injury.
Main Methods:
- Male C57BL/6 mice underwent 30 minutes of bilateral renal ischemia followed by reperfusion or sham operation.
- Oligonucleotide microarrays were used to analyze mRNA expression for approximately 10,000 genes up to 4 days post-I/R.
- Real-time quantitative RT-PCR was employed to validate expression changes for selected genes.
Main Results:
- Significant alterations in gene expression were observed at day 1 and day 4 post-I/R.
- Over 50 genes were upregulated more than 4-fold, and over 70 genes were downregulated to less than 25% of baseline by day 1.
- Induced transcripts were primarily associated with cell structure, extracellular matrix, intracellular calcium binding, and cell division/differentiation.
Conclusions:
- Ischemia-reperfusion injury triggers widespread changes in gene expression in the kidney.
- Several novel genes identified in this study may play critical roles in the renal repair process after ischemic insult.

