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Project

Mir-210 at the crossroad of M2 and M1 macrophage polarization: relevance for sepsis and cancer.

Tissue hypoxia, which occurs during various pathophysiological conditions, concomitantly alters thecellular response to promote restoration of oxygen homeostasis. However the respective response to a hypoxic insult varies between different disease types as it is additionally shaped by other environmental cues. For instance macrophages elicit a pro-inflammatory (M1-like) phenotype during LPS induced sepsis (a hypoxia associated condition), but exhibit a pro-tumoral, proangiogenic (M2-like) phenotype when exposed to the hypoxic tumor environment. By genome-wide expression analysis in mouse macrophages we identified mir-210 at the crossroad of hypoxia induced signaling pathways, as its expression level determines their phenotypic skewing. mir-210 is highly upregulated by hypoxia in this cell type. Interestingly, in the presence of tumor secreted M2 cytokines the hypoxic upregulation of mir-210 is reversed and accompanied by a skewing of macrophages to an M2-like phenotype. Conversely hypoxia and pro-inflammatory stimuli such as LPS potentiate an M1-like phenotype. Thus with the tumor model on one hand and LPS induced inflammation on the other we aim to delineate how M1 and M2 cytokines might shape the macrophage phenotype via modulation of mir-210 expression and thus regulate disease progression. In a next step we will further investigate how microvesicle transfer of mir-210 influences the disease outcome and if it might offer new possibilities for therapeutical interventions.

Date:1 Jan 2015 →  31 Dec 2017
Keywords:sepsis, kanker, macrofaag polarisatie
Disciplines:Diagnostics, Laboratory medicine, Medicinal products