Soluble CD74 Reroutes MIF/CXCR4/AKT-Mediated Survival of Cardiac Myofibroblasts to Necroptosis

Soppert, Josefin
Kraemer, Sandra
Beckers, Christian
Averdunk, Luisa
Möllmann, Julia
Denecke, Bernd
Götzenich, Andreas
Marx, Gernot
Bernhagen, Jürgen
Stoppe, Christian

Open PDF

Open link

Publication date

January 2018

DOI

10.1161/JAHA.118.009384

Publisher

Ludwig-Maximilians-Universität München

Abstract

Background: Although macrophage migration inhibitory factor (MIF) has been demonstrated to mediate cardioprotection in ischemia/reperfusion injury and antagonize fibrotic effects through its receptor, CD74, the function of the soluble CD74 receptor ectodomain (sCD74) and its interaction with circulating MIF have not been explored in cardiac disease. Methods and Results: Cardiac fibroblasts were isolated from hearts of neonatal mice and differentiated into myofibroblasts. Co-treatment with recombinant MIF and sCD74 induced cell death (P<0.001), which was mediated by receptor-interacting serine/threonine-protein kinase (RIP) 1/RIP3-dependent necroptosis (P=0.0376). This effect was specific for cardiac fibroblasts and did not affect cardiomyoc...