Department of Nephrology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
Department of Radiotherapy, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.
Technol Health Care. 2024;32(6):4743-4756. doi: 10.3233/THC-241175.
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.
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).
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.
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).
CTX upregulates the expression of miR-223, promotes polarization of M2 macrophages, alleviates the inflammatory response and renal injury of MN.
膜性肾病（MN），又称膜性肾小球肾炎，是成人肾病综合征的主要病因。主要的病理特征包括免疫复合物在肾小球基底膜上皮细胞内沉积、基底膜增厚和足突融合。
本研究旨在探讨免疫和炎症调节剂 miR-223 在环磷酰胺（CTX）对膜性肾病（MN）的免疫抑制和抗炎作用中的作用。
用 miR-223 模拟物或抑制剂调节 miR-223 水平。LPS 诱导炎症细胞模型和细胞极化。CTX 用于治疗脂多糖（LPS）诱导的炎症反应和极化。阳离子牛血清白蛋白（c-BSA）诱导 BALB/c 小鼠 MN 模型，CTX 用于治疗 c-BSA 诱导的 MN。
LPS 诱导的炎症模型细胞中的 miR-223 水平低于对照细胞。LPS+miR-223 模拟物和 CTX+miR-223i 细胞中的炎症因子水平低于 LPS 和 miR-223i 细胞。LPS+miR-223 模拟物、CTX+miR-223i 巨噬细胞 M2 表型标志物精氨酸酶-1（Arg1）、转化生长因子β1（TGF-β1）、抗炎因子白细胞介素-4（IL4）和白细胞介素-13（IL13）的蛋白水平明显高于 LPS 和 miR-223i。CTX 在阳离子牛血清白蛋白（c-BSA）诱导的 BALB/c 小鼠 MN 模型中得到了证实。
CTX 上调 miR-223 的表达，促进 M2 巨噬细胞的极化，减轻 MN 的炎症反应和肾损伤。
