Increased expression of the proprotein convertase enzyme FURIN in rheumatoid arthritis

Abstract

FURIN is a proprotein convertase enzyme that inhibits the pro-inflammatory function of T cells and myeloid cells. Previously, elevated FURIN expression levels have been reported in immune-mediated diseases, such as primary Sjögren's syndrome. Here, we investigated the levels of FURIN in peripheral blood (PB) and synovial fluid (SF) leukocytes from patients with rheumatoid arthritis (RA). Methods FURIN mRNA expression in PB and SF cells was determined by qRT-PCR and FURIN plasma levels were measured using ELISA. Associations between FURIN levels and demographic and clinical characteristics of the patients were determined. Results FURIN levels were significantly elevated in PB and SF mononuclear cells, T cells and monocytes from RA patients when compared to healthy controls. High FURIN levels were significantly associated with the prevailing prednisolone treatment, higher prednisolone doses as well as increased CRP levels and Health Assessment Questionnaire (HAQ) values. Conclusion FURIN is significantly upregulated in RA PB and SF leukocytes, suggesting that FURIN may have a role in the pathogenesis of RA. In addition, our results suggest that elevated FURIN expression is associated with the indicators of more severe RA.

Pan-Cancer Analysis of FURIN as a Potential Prognostic and Immunological Biomarker

“…Furin and other PCs process a large number of precursor proteins, such as hormones, neuropeptides, growth factors and their receptors, bacterial toxins, and adhesion molecule, through various secretory pathways (Seidah and Prat, 2012). Thus, the deregulation of FURIN is correlated with a variety of pathological conditions, including cardiovascular disease (Yakala et al, 2019), rheumatoid disease (Valli et al, 2019), endocrinopathies (Al Rifai et al, 2017), and central nervous system disorder (Yang et al, 2018). As for cancers, several studies have found that FURIN is expressed in various cancers and sarcomas (Khatib et al, 2002;Coppola et al, 2008;Lee et al, 2016;Jaaks and Bernasconi, 2017).…”

Increased FURIN expression in rheumatoid arthritis patients and its anti‐inflammatory effect

“…In our study, no correlation was observed between FURIN and disease activity in RA patients; this is consistent with a current research suggesting that FURIN levels in peripheral blood were not associated with ESR and CRP. Valli et al18 demonstrated that elevated FURIN expression indicated the severity of RA and that the FURIN levels positively correlate with prednisolone treatment. However, we found that the levels of FURIN in the prednisolone treatment group were relatively lower but with no statistic difference(Table S2).…”

FURIN regulates cytotoxic T‐lymphocyte effector function and memory cell transition in mice

“…Altered expression levels of FURIN have been associated with human malignancies including lung and skin cancers [5,6] as well as with autoimmune diseases such as Sjögren's syndrome and rheumatoid arthritis [37,38]. In fact, cell therapy where a combination of granulocyte-macrophage colony stimulating factor (GMCSF) cDNA and a shRNA construct against FURIN (Vigil, Gradalis) are transfected into autologous tumor cells is currently being evaluated in phase I-III clinical trials against human gyneco- In panels (A) and (C), the statistical evaluation of differences was done using DESeq2 and adjusted using the Benjamini-Hochberg method.…”