FURIN_U937_study

Data relating to CRISPR mediated FURIN depletion in U937 cells The pro-protein convertase FURIN (PCSK3) is implicated in a wide range of normal as well as pathological biological processes such as infectious disease, cancer and cardiovascular disease. Previously, we performed a systemic inhibition of FURIN in a mouse model of atherosclerosis and demonstrated significant alterations in plaque reduction and macrophage function attending FURIN inhibition. To understand the cellular mechanisms affected by FURIN inhibition in myeloid cells, we optimized a CRISPR-mediated gene deletion protocol for successfully deriving hemizygous (HZ) and nullizygous (NZ) FURIN knockout clones in U937 monocytic cells using lipotransfection based procedures and a dual guide RNA delivery strategy. We observed important differences in basic monocyte and macrophage functions such as phagocytosis, lipid accumulation, cell migration, inflammatory gene expression, cytokine release patterns, cytokine secretion and whole-genome gene expression between wild-type, HZ and NZ FURIN clones. These studies provide a mechanistic basis on the possible roles of myeloid cell FURIN in cardiovascular disorders.