Glomerular endothelial expression of type I IFN-stimulated gene, DExD/H-Box helicase 60 via toll-like receptor 3 signaling: possible involvement in the pathogenesis of lupus nephritis. Issue 1 (31st December 2022)

• Record Type: Journal Article
• Authors: Karasawa, Takao; Sato, Riko; Imaizumi, Tadaatsu; Hashimoto, Shun; Fujita, Masashi; Aizawa, Tomomi; Tsugawa, Koji; Kawaguchi, Shogo; Seya, Kazuhiko; Terui, Kiminori; Tanaka, Hiroshi
• Is Part Of: Renal failure. Volume 44:Issue 1(2022)
• Page Start: 137
• Page End: 145
• Publication Date: 2022-12-31
• Subjects: Poly (ADP-ribose) polymerase (PARP) -- DExD/H-Box Helicase 60 (DDX60) -- Glomerular endothelial cells -- lupus nephritis -- toll-like receptor; Chronic renal failure -- Periodicals; Acute renal failure -- Periodicals; Uremia -- Periodicals; 616.614005
• DOI: 10.1080/0886022X.2022.2027249
• Languages: English
• ISSNs: 0886-022X

Abstract

Abstract: Background: Sustained type I interferon (IFN) activation via Toll-like receptor (TLR) 3, 7 and 9 signaling has been reported to play a pivotal role in the development of lupus nephritis (LN). Although type I IFN activation has been shown to induce interferon-stimulated genes (ISGs) expression in systemic lupus erythematosus, the implication of ISGs expression in intrinsic glomerular cells remains largely unknown. Methods: We treated cultured human glomerular endothelial cells (GECs) with polyinosinic-polycytidylic acid (poly IC), R848, and CpG (TLR3, TLR7, and TLR9 agonists, respectively) and analyzed the expression of DExD/H-Box Helicase 60 (DDX60), a representative ISG, using quantitative reverse transcription-polymerase chain reaction and western blotting. Additionally, RNA interference against IFN-β or DDX60 was performed. Furthermore, cleavage of caspase 9 and poly (ADP-ribose) polymerase (PARP), markers of cells undergoing apoptosis, was examined using western blotting. We conducted an immunofluorescence study to examine endothelial DDX60 expression in biopsy specimens from patients with LN. Results: We observed that endothelial expression of DDX60 was induced by poly IC but not by R848 or CpG, and RNA interference against IFN-β inhibited poly IC-induced DDX60 expression. DDX60 knockdown induced cleavage of caspase 9 and PARP. Intense endothelial DDX60 expression was observed in biopsy specimens from patients with diffuse proliferative LN. Conclusion: Glomerular endothelial DDX60 expression may prevent apoptosis, which is involved in the pathogenesis of LN. Modulating the upregulation of the regional innate immune system via TLR3 signaling may be a promising treatment target for LN.