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Macrophage migration inhibitory factor promotes renal injury induced by ischemic reperfusion.


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-?B signalling as mice lacking MIF were protected from AKI by largely suppressing CD74/TLR-4-NF-?B associated renal inflammation, including the expression of MCP-1, TNF-?, IL-1?, 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.

SUBMITTER: Li JH 

PROVIDER: S-EPMC6533527 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Macrophage migration inhibitory factor promotes renal injury induced by ischemic reperfusion.

Li Jin H JH   Tang Ying Y   Lv Jun J   Wang Xiao H XH   Yang Hui H   Tang Patrick M K PMK   Huang Xiao R XR   He Zhi J ZJ   Zhou Zi J ZJ   Huang Qiu Y QY   Klug Jörg J   Meinhardt Andreas A   Fingerle-Rowson Günter G   Xu An P AP   Zheng Zhi H ZH   Lan Hui Yao HY  

Journal of cellular and molecular medicine 20190409 6


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 cr  ...[more]

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