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Updated: Jan 26, 2026
An Effective Mouse Model of Unilateral Renal Ischemia-Reperfusion Injury
Published on: July 15, 2021
Macrophage migration inhibitory factor promotes renal injury induced by ischemic reperfusion
Jin H Li1,2, Ying Tang3, Jun Lv3
1Department of Nephrology, The Seventh Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, China.
Abstract:
Macrophage migration inhibitory factor (MIF) is pleiotropic cytokine that has multiple effects in many inflammatory and immune diseases. This study reveals a potential role of MIF in acute kidney injury (AKI) in patients and in kidney ischemic reperfusion injury (IRI) mouse model in MIF wild-type (WT) and MIF knockout (KO) mice. Clinically, plasma and urinary MIF levels were largely elevated at the onset of AKI, declined to normal levels when AKI was resolved and correlated tightly with serum creatinine independent of disease causes. Experimentally, MIF levels in plasma and urine were rapidly elevated after IRI-AKI and associated with the elevation of serum creatinine and the severity of tubular necrosis, which were suppressed in MIF KO mice. It was possible that MIF may mediate AKI via CD74/TLR4-NF-κB signalling as mice lacking MIF were protected from AKI by largely suppressing CD74/TLR-4-NF-κB associated renal inflammation, including the expression of MCP-1, TNF-α, IL-1β, IL-6, iNOS, CXCL15(IL-8 in human) and infiltration of macrophages, neutrophil, and T cells. In conclusion, our study suggests that MIF may be pathogenic in AKI and levels of plasma and urinary MIF may correlate with the progression and regression of AKI.
Insights
Macrophage migration inhibitory factor (MIF) drives acute kidney injury (AKI). Lowering MIF levels protected against kidney damage by reducing inflammation and improving outcomes in both patients and a mouse model.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Background:
- Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine implicated in various inflammatory and immune diseases.
- The specific role of MIF in acute kidney injury (AKI) has not been fully elucidated.
- Understanding MIF's function in AKI is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the role of MIF in the pathogenesis of acute kidney injury (AKI).
- To examine the correlation between MIF levels and AKI severity in clinical and experimental settings.
- To explore the underlying molecular mechanisms by which MIF contributes to AKI.
Main Methods:
- Clinical analysis of plasma and urinary MIF levels in AKI patients.
- Experimental induction of kidney ischemic reperfusion injury (IRI) in wild-type (WT) and MIF knockout (KO) mice.
- Assessment of renal inflammation markers, immune cell infiltration, and signaling pathways (CD74/TLR4-NF-κB).
Main Results:
- Elevated plasma and urinary MIF levels in AKI patients correlated with serum creatinine and disease severity.
- Mice lacking MIF (KO) showed suppressed renal inflammation, reduced tubular necrosis, and protected kidney function after IRI-AKI.
- MIF deficiency attenuated the CD74/TLR4-NF-κB signaling pathway, decreasing pro-inflammatory cytokine expression and immune cell infiltration.
Conclusions:
- MIF plays a pathogenic role in acute kidney injury.
- Plasma and urinary MIF levels serve as potential biomarkers for AKI progression and resolution.
- Targeting MIF or its signaling pathway may offer a therapeutic strategy for AKI.
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