Affiliations: [a] Department of Nephrology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China | [b] Department of Radiotherapy, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China
Correspondence:
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Corresponding author: Chunying Yao, Department of Nephrology, The Third Affiliated Hospital of Qiqihar Medical University, No.27 Taishun Street, Tiefeng District, Qiqihar, Heilongjiang 161000, China. E-mails: [email protected]; yaochunying @qqheyxyfsdsyy.wecom.work.
Abstract: BACKGROUND: Membranous nephropathy (MN), also known as membranous glomerulonephritis, is a leading cause of adult nephrotic syndrome. The main pathological features encompass the deposition of immune complexes within the glomerular basement membrane epithelial cells, thickening of the basement membrane, and fusion of the foot process. OBJECTIVE: This study aims to investigate the role of the immune and inflammatory modulator miR-223 in the immunosuppressive and anti-inflammatory effects of cyclophosphamide (CTX) on membranous nephropathy (MN). METHODS: miR-223 mimetics or inhibitors was used to regulate miR-223 levels. LPS induced inflammatory cell model and cell polarization. CTX was used to treat Lipopolysaccharides (LPS) induced inflammatory response and polarization. Cationic bovine serum albumin (c-BSA) induced BALB/c mouse MN model, while CTX was used to treat c-BSA induced MN. RESULTS: The miR-223 level in LPS induced inflammatory model cells was lower than that in control cells. The levels of inflammatory factors in LPS+miR-223 mimetics and CTX+miR-223i cells were lower than those in LPS and miR-223i cells. The protein levels of LPS+miR-223 mimic, CTX+miR-223i macrophage M2 phenotype markers Arginase-1 (Arg1), transforming growth factor β1 (TGF-β1), anti-inflammatory factors interleukin-4 (IL4) and interleukin-13 (IL13) were significantly higher than those of LPS and miR-223i. The effect of CTX was confirmed in a BALB/c mouse MN model induced by cationic bovine serum albumin (c-BSA). CONCLUSION: CTX upregulates the expression of miR-223, promotes polarization of M2 macrophages, alleviates the inflammatory response and renal injury of MN.
