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Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Transcriptional progressive patterns from mild to severe renal ischemia/reperfusion-induced kidney injury in mice
Dong Lai1, Lei Wang1, Jia-Rui Li2
1Department of Urology, The Third Medical Center, Chinese PLA General Hospital, Beijing, China.
Abstract:
The renal ischemia/reperfusion (I/R)-induced acute kidney injury incidence after nephron-sparing surgery for localized renal tumors is 20%, but the biological determinant process of postoperative acute kidney injury remains unclear. Using Gene Expression Omnibus database (GSE192883) and several bioinformatics analyses (discrete time points analysis, gene set enrichment analysis, dynamic network biomarker analysis, etc), combined with the establishment of the I/R model for verification, we identified three progressive patterns involving five core pathways confirmed using gene set enrichment analysis and six key genes (S100a10, Pcna, Abat, Kmo, Acadm, and Adhfe1) verified using quantitative polymerase chain reaction The dynamic network biomarker (DNB) subnetwork composite index value is the highest in the 22-min ischemia group, suggesting the transcriptome expression level fluctuated sharply in this group, which means 22-min ischemia is an critical warning point. This study illustrates the core molecular progressive patterns from mild to severe I/R kidney injury, laying the foundation for precautionary biomarkers and molecular intervention targets for exploration. In addition, the safe renal artery blocking time of nephron-sparing surgery that we currently accept may not be safe anymore.
Insights
Acute kidney injury (AKI) after surgery is unclear. This study identifies key genes and pathways in AKI progression, revealing 22-minute ischemia as a critical warning point for kidney damage.
Area of Science:
- Nephrology
- Molecular Biology
- Bioinformatics
Background:
- Acute kidney injury (AKI) occurs in 20% of patients undergoing nephron-sparing surgery for renal tumors.
- The biological mechanisms driving postoperative AKI remain poorly understood.
Purpose of the Study:
- To elucidate the molecular progression patterns of renal ischemia/reperfusion (I/R)-induced AKI.
- To identify potential biomarkers and therapeutic targets for AKI prevention and treatment.
Main Methods:
- Utilized the Gene Expression Omnibus database (GSE192883) for bioinformatics analysis.
- Performed discrete time points analysis, gene set enrichment analysis, and dynamic network biomarker analysis.
- Validated findings using an I/R animal model and quantitative polymerase chain reaction.
Main Results:
- Identified three progressive patterns of I/R kidney injury.
- Confirmed five core pathways and six key genes (S100a10, Pcna, Abat, Kmo, Acadm, Adhfe1) involved in AKI.
- Determined that 22-minute ischemia represents a critical warning point with sharp transcriptome fluctuations.
Conclusions:
- This study provides insights into the molecular basis of AKI progression.
- The findings lay the groundwork for developing novel biomarkers and molecular interventions for AKI.
- Current accepted renal artery clamping times during surgery may require re-evaluation.
