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Updated: Jun 23, 2025

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
Published on: November 10, 2021
RGC-32 mediates proinflammatory and profibrotic pathways in immune-mediated kidney disease
Alexandru Tatomir1, Sonia Vlaicu2, Vinh Nguyen3
1Department of Neurology, University of Maryland School of Medicine, Baltimore, MD, USA; Neurology Service, Veterans Administration Medical Health Care Center, Baltimore, MD, USA.
Abstract:
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.
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