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Updated: Sep 13, 2025
Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration
Published on: June 7, 2014
Biphasic protective effects of macrophage migration inhibitory factor in ischemia/reperfusion-induced acute kidney
Yiwei Du1,2, Chunni Feng1, Lu Zhou1
1Department of Nephrology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
Abstract:
Ferroptosis is involved in the occurrence and progression of renal ischemia/reperfusion (I/R) injury. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that is closely associated with kidney diseases. However, the underlying mechanisms between MIF and ferroptosis in acute kidney injury (AKI) still remain unclear. In contrast to conventional strategies, we further investigate the dynamic expression and role of MIF in both ischemic and reperfusion phases. In the present study, we establish hypoxia/reoxygenation (H/R) and I/R induced AKI models, verify ferroptosis by detecting pro-ferroptotic changes and associated indicators, and use si-RNA or Adeno-Associated virus (AAV) to knock down the expression of MIF, observing subsequent changes of ferroptosis. The results show that treatment with recombinant MIF reduces lipid ROS generation and MDA levels, upregulating glutathione (GSH) levels, with increasing AMP-activated protein kinase (AMPK) phosphorylation. While the deficiency of MIF blunted its protective effect on renal tubular epithelial cells, which demonstrates that MIF ameliorates ferroptosis injury via activating the AMPK pathway in the ischemia stage and increasing GSH content in the reperfusion stage. In conclusion, our results suggest the nephroprotective role of MIF in inhibiting ferroptosis and provide insight into the prevention and treatment of AKI.
Insights
Macrophage migration inhibitory factor (MIF) protects against ferroptosis in acute kidney injury (AKI). MIF activates the AMPK pathway during ischemia and increases glutathione during reperfusion, offering a potential therapeutic strategy for AKI.
Area of Science:
- Nephrology
- Cellular Biology
- Biochemistry
Background:
- Ferroptosis, a form of regulated cell death, plays a role in renal ischemia/reperfusion (I/R) injury.
- Macrophage migration inhibitory factor (MIF) is linked to kidney diseases, but its role in ferroptosis during acute kidney injury (AKI) is not fully understood.
Purpose of the Study:
- To investigate the dynamic expression and function of MIF during both ischemic and reperfusion phases of AKI.
- To elucidate the underlying mechanisms of MIF in regulating ferroptosis in AKI.
Main Methods:
- Established hypoxia/reoxygenation (H/R) and I/R-induced AKI models.
- Verified ferroptosis by assessing pro-ferroptotic markers.
- Utilized siRNA and Adeno-Associated virus (AAV) to knockdown MIF expression.
- Analyzed lipid reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and AMP-activated protein kinase (AMPK) phosphorylation.
Main Results:
- Recombinant MIF treatment reduced lipid ROS and MDA levels, while increasing GSH and AMPK phosphorylation.
- MIF deficiency impaired its protective effects on renal tubular epithelial cells.
- MIF ameliorates ferroptosis injury by activating the AMPK pathway during ischemia and increasing GSH during reperfusion.
Conclusions:
- MIF exhibits a nephroprotective role in inhibiting ferroptosis during AKI.
- MIF's protective effects involve activating the AMPK pathway and modulating GSH levels.
- Findings provide insights into potential therapeutic strategies for AKI prevention and treatment.
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