RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease.

Autor: Tatomir A; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA; Neurology Service, Veterans Administration Medical Health Care Center, Baltimore, MD, USA., Vlaicu S; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Internal Medicine, Medical Clinic nr. 1, 'Iuliu Hatieganu' University of Medicine and Pharmacy, Cluj-Napoca, Romania., Nguyen V; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA., Luzina IG; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA., Atamas SP; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA., Drachenberg C; Department of Pathology, University of Maryland School of Medicine, USA., Papadimitriou J; Department of Pathology, University of Maryland School of Medicine, USA., Badea TC; Research and Development Institute, Faculty of Medicine, Transylvania University of Brasov, Brasov, Romania., Rus HG; Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA; Neurology Service, Veterans Administration Medical Health Care Center, Baltimore, MD, USA., Rus V; Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: vrus@som.umaryland.edu.
Jazyk: angličtina
Zdroj: Clinical immunology (Orlando, Fla.) [Clin Immunol] 2024 Aug; Vol. 265, pp. 110279. Date of Electronic Publication: 2024 Jun 13.
DOI: 10.1016/j.clim.2024.110279
Abstrakt: Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFβ and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17 + and IFNγ + cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.
Competing Interests: Declaration of competing interest None of the authors has any financial conflict of interest to disclose.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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