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

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, CD 74, the function of the soluble CD 74 receptor ectodomain ( sCD 74) 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 sCD 74 induced cell death ( P<0.001), which was mediated by receptor-interacting serine/threonine-protein kinase ( RIP) 1/ RIP 3-dependent necroptosis ( P=0.0376). This effect was specific for cardiac fibroblasts and did not affect cardiomyocytes. Gene expression analyses using mic

SUBMITTER: Soppert J 

PROVIDER: S-EPMC6201423 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature