MIF in kidney diseases : A story of Dr. Jekyll and Mr. Hyde.

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MIF in kidney diseases : A story of Dr. Jekyll and Mr. Hyde.

Pathologe. 2018 Dec 19;:

Authors: Boor P

Abstract
BACKGROUND: Macrophage migration-inhibitory factor (MIF) is a cytokine best known for its proinflammatory and disease-aggravating role in a number of conditions, including atherosclerosis, autoimmune diseases, sepsis, and glomerulonephritides.
OBJECTIVES: In our studies we aimed to define the role of MIF on local renal resident cells, in particular the renal epithelium.
RESULTS: We have shown that MIF exerts local effects on glomerular cells, in particular the parietal epithelial cells and mesangial cells, promoting their pathological proliferation and aggravating disease course of a murine model of immune-mediated glomerulonephritis. In contrast, in a large set of animal and in vitro experiments, we have shown that in the setting of chronic kidney disease, MIF had an unexpected and potent antifibrotic and anti-inflammatory effect. This was mediated by enhanced regeneration and reduced cell-cycle arrest of tubular epithelial cells. Finally, in a combined approach using clinical studies, animal models, and in vitro experiments, we have shown that MIF is also renoprotective in the setting of acute kidney injury. In this setting, MIF-modulated programmed cell death of tubular cells and thereby reduced necroinflammation and kidney injury.
CONCLUSIONS: Taken together, MIF has a dual role in kidney diseases, promoting (auto)immune glomerular diseases and limiting tubular cell injury in the setting of acute and chronic kidney diseases. These data suggest potential safety issues of systemic MIF targeted therapies, but also open new therapeutic options by targeting MIF or its analogues to tubular cells.

PMID: 30569239 [PubMed - as supplied by publisher]

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