MIF, CD74 and other partners in kidney disease: tales of a promiscuous couple

M D Sanchez-Niño; A B Sanz; O Ruiz-Andres; J Poveda; M C Izquierdo; R Selgas; J Egido; A Ortiz

doi:10.1016/j.cytogfr.2012.08.001

MIF, CD74 and other partners in kidney disease: tales of a promiscuous couple

Cytokine Growth Factor Rev. 2013 Feb;24(1):23-40. doi: 10.1016/j.cytogfr.2012.08.001. Epub 2012 Sep 7.

Authors

M D Sanchez-Niño¹, A B Sanz, O Ruiz-Andres, J Poveda, M C Izquierdo, R Selgas, J Egido, A Ortiz

Affiliation

¹ IDIPaz, Servicio de Nefrologia, Madrid, Spain. mdsanchez@fjd.es

PMID: 22959722
DOI: 10.1016/j.cytogfr.2012.08.001

Abstract

Macrophage migration inhibitory factor (MIF) is increased in kidney and urine during kidney disease. MIF binds to and activates CD74 and chemokine receptors CXCR2 and CXCR4. CD74 is a protein trafficking regulator and a cell membrane receptor for MIF, D-dopachrome tautomerase (D-DT/MIF-2) and bacterial proteins. MIF signaling through CD74 requires CD44. CD74, CD44 and CXCR4 are upregulated in renal cells in diseased kidneys and MIF activation of CD74 in kidney cells promotes an inflammatory response. MIF or CXCR2 targeting protects from experimental kidney injury, CD44 deficiency modulates kidney injury and CXCR4 activation promotes glomerular injury. However, the contribution of MIF or MIF-2 to these actions of MIF receptors has not been explored. The safety and efficacy of strategies targeting MIF, CD74, CD44 and CXCR4 are under study in humans.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antigens, Differentiation, B-Lymphocyte / metabolism*
Histocompatibility Antigens Class II / metabolism*
Humans
Hyaluronan Receptors / metabolism
Inflammation
Intramolecular Oxidoreductases / metabolism*
Intramolecular Oxidoreductases / urine
Kidney Diseases / metabolism*
Macrophage Migration-Inhibitory Factors / metabolism*
Macrophage Migration-Inhibitory Factors / urine
Mice
Receptors, CXCR4 / metabolism
Receptors, Cell Surface / metabolism
Receptors, Interleukin-8B / metabolism

Substances

Antigens, Differentiation, B-Lymphocyte
CD44 protein, human
CXCR4 protein, human
Histocompatibility Antigens Class II
Hyaluronan Receptors
Macrophage Migration-Inhibitory Factors
Receptors, CXCR4
Receptors, Cell Surface
Receptors, Interleukin-8B
invariant chain
Intramolecular Oxidoreductases
MIF protein, human
dopachrome isomerase