title: MIF, CD74 and other partners in kidney disease: tales of a promiscuous couple.
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.
authors.affiliation: IDIPaz, Servicio de Nefrologia, Madrid, Spain. mdsanchez@fjd.es
authors.forename: M D
authors.initials: MD
authors.lastname: Sanchez-Niño
authors.forename: A B
authors.initials: AB
authors.lastname: Sanz
authors.forename: O
authors.initials: O
authors.lastname: Ruiz-Andres
authors.forename: J
authors.initials: J
authors.lastname: Poveda
authors.forename: M C
authors.initials: MC
authors.lastname: Izquierdo
authors.forename: R
authors.initials: R
authors.lastname: Selgas
authors.forename: J
authors.initials: J
authors.lastname: Egido
authors.forename: A
authors.initials: A
authors.lastname: Ortiz
mesh_terms: D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007249:Inflammation; D019746:Intramolecular Oxidoreductases / Q000378:metabolism* / Q000652:urine; D007674:Kidney Diseases / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism* / Q000652:urine; D051379:Mice; D019718:Receptors, CXCR4 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; C497483:CD44 protein, human; C527276:CXCR4 protein, human; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; D008263:Macrophage Migration-Inhibitory Factors; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D023063:Receptors, Interleukin-8B; C045084:invariant chain; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C042501:dopachrome isomerase