Proprotein convertases in human atherosclerotic plaques: The overexpression of FURIN and its substrate cytokines BAFF and APRIL

The Proprotein Convertase Subtilisin/Kexin FurinA Regulates Zebrafish Host Response against Mycobacterium marinum

“…Previously, we and others have shown that FURIN is predominantly expressed in Th1 cells and that FURIN expression is induced in activated CD4 ϩ T lymphocytes and myeloid cells (14)(15)(16)(17). Our functional analyses using mice with a tissue-specific deletion of Furin in T cells (CD4cre-fur fl/fl ) further demonstrated that FURIN is essential for the adequate maturation of pro-TGFB1 and for T regulatory (Treg) cell-mediated immune suppression in vivo (18).…”

“…Our data show that furinA/FURIN expression is upregulated in the host in response to a mycobacterial infection and the Th1 hallmark cytokine IL-12 (15). FURIN is also secreted from macrophages in response to LPS activation (14), and it can be measured from serum (66). Therefore, in the future it will be interesting to assess whether serum FURIN levels can be used as an infection biomarker to mirror mycobacterial growth and the activation of Th1 type immune responses.…”

“…1A). Previously, in vitro analyses have shown that FURIN expression is upregulated as a result of CD4 ϩ T cell activation and in lipopolysaccharide (LPS)-stimulated CD14 ϩ myeloid cells (14,15). In accordance with this, the M. marinum infection caused an induction in furinA mRNA expression in both furinA td204e/ϩ (1.6-fold at 4 wpi, P ϭ 0.02, and 4.9-fold at 9 wpi, P Ͻ 0.001) and WT zebrafish (1.7-fold at 4 wpi, not significant [NS], P ϭ 0.11; 3.4-fold at 9 wpi, P Ͻ 0.001) demonstrating that immune activation in vivo upregulates this convertase.…”

Proprotein convertase furin/PCSK3 and atherosclerosis: New insights and potential therapeutic targets

“…It was reported that embryos lacking furin die between days 10.5 and 11.5, likely resulting from severe ventral closure defects and hemodynamic insufficiency associated with the failure of the heart tube morphogenesis formation [6,7]. Evidence suggests that furin participates in the initiation and progression of atherosclerosis by regulating inflammatory response, lipid metabolism and blood pressure (BP) [8,9]. Recently, a large-scale association analysis has identified the single nucleotide polymorphism (SNP) of furin gene (rs17514846) as a new risk locus for CAD [10].…”

60 YEARS OF POMC: From the prohormone theory to pro-opiomelanocortin and to proprotein convertases (PCSK1 to PCSK9)

“…biological ramifications of these enzymes in heath and disease. Multiple studies have demonstrated association between genetic variations of PCs and various human health conditions: PC1/3 and PC2 in obesity and diabetes (Zheng et al 2012, Nead et al 2015; furin in atherosclerosis (Turpeinen et al 2011); PC5/6 and mostly PCSK9 in cholesterol metabolism (Iatan et al 2009, Wu & Li 2014, a review); PC7 in iron metabolism (Oexle et al 2011). Ex vivo and in vitro as well as animal studies have implicated these enzymes in cancer (Mbikay et al 1997, Khatib et al 2002, in vascular remodeling (Stawowy 2015, reviews), and viral diseases (Pasquato et al 2013, a review).…”