1. Macrophage migration inhibitory factor promotes renal injury induced by ischemic reperfusion
- Author
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Jun Lv, Zhi H. Zheng, Zi J Zhou, Hui Yang, Qiu Y. Huang, Xiao H. Wang, Andreas Meinhardt, Jörg Klug, Hui-Yao Lan, Patrick Ming-Kuen Tang, Gunter Fingerle-Rowson, Ying Tang, Jin H Li, Xiao R. Huang, Zhi J. He, and An P. Xu
- Subjects
Male ,0301 basic medicine ,CD74 ,medicine.medical_treatment ,Kidney ,urologic and male genital diseases ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Chemokine CCL2 ,Mice, Knockout ,NF-kappa B ,Acute kidney injury ,Acute Kidney Injury ,Middle Aged ,female genital diseases and pregnancy complications ,Intramolecular Oxidoreductases ,Cytokine ,medicine.anatomical_structure ,Creatinine ,Reperfusion Injury ,030220 oncology & carcinogenesis ,Disease Progression ,Molecular Medicine ,Original Article ,Female ,renal inflammation ,Adult ,medicine.medical_specialty ,Urinary system ,chemical and pharmacologic phenomena ,macrophage migration inhibitory factor (MIF) ,03 medical and health sciences ,Internal medicine ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,Macrophage Migration-Inhibitory Factors ,CXCL15 ,Aged ,urogenital system ,business.industry ,Histocompatibility Antigens Class II ,Original Articles ,Cell Biology ,medicine.disease ,cytokines ,Antigens, Differentiation, B-Lymphocyte ,Mice, Inbred C57BL ,Toll-Like Receptor 4 ,Disease Models, Animal ,030104 developmental biology ,Endocrinology ,chemistry ,Macrophage migration inhibitory factor ,business - 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.
- Published
- 2019
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