肾纤维化是慢性肾病 (CKD) 的主要病理特征。虽然已报道莪术具有抗纤维化作用，但其对微小RNA (miRNA)-调控的肾纤维化机制影响尚不清楚。本研究建立了单侧输尿管梗阻 (UUO) 模型和转化生长因子 (TGF)-β1 诱导的正常大鼠肾小管上皮细胞系 (NRK-52E) 模型，研究了莪术对肾纤维化及其miRNA/靶基因机制的保护作用。在HEK293细胞中进行双荧光素酶检测以确认miRNA和靶基因的直接结合。结果表明，口服莪术显著改善了UUO小鼠的体重损失和生理化学参数的增加，包括血清尿酸、肌酐和尿素氮。炎症因子，包括肿瘤坏死因子-α、单核细胞趋化蛋白-1和白细胞介素 (IL)-1β，但不包括IL-6，均被莪术下调。莪术降低了TGF-β1和纤维化相关蛋白，包括α-平滑肌肌动蛋白、IV型胶原和纤维连接蛋白的表达水平，增加了E-钙黏蛋白的表达。此外，miR-490-3p 在 UUO 小鼠中降低，与高迁移蛋白A2表达升高呈负相关。我们进一步证实了高迁移蛋白A2是miR-490-3p的靶标。转染miR-490-3p模拟物降低了TGF-β1诱导的NRK-52E细胞中纤维化相关蛋白和HMGA2的表达水平，而转染miR-490-3p抑制剂升高了它们的表达水平。此外，转染miR-490-3p模拟物增强了莪术的抗纤维化作用，而转染miR-490-3p抑制剂则取消了莪术的保护作用。因此，作为莪术在依赖HMGA2信号通路中预防肾纤维化的新靶标，miR-490-3p 在 CKD 病理学中具有潜在的意义。Copyright © 2023 Wang、Wang、Li、Zhou、Wang、Long、Wang、Li、Huang 和 Ba。

Renal fibrosis is a major pathological feature of chronic kidney disease (CKD). While emodin is reported to elicit anti-fibrotic effects on renal injury, little is known about its effects on microRNA (miRNA)-modulated mechanisms in renal fibrosis. In this study, we established a unilateral ureteral obstruction (UUO) model and a transforming growth factor (TGF)-β1-induced normal rat renal tubular epithelial cell line (NRK-52E) model to investigate the protective effects of emodin on renal fibrosis and its miRNA/target gene mechanisms. Dual-luciferase assay was performed to confirm the direct binding of miRNA and target genes in HEK293 cells. Results showed that oral administration of emodin significantly ameliorated the loss of body weight and the increase in physicochemical parameters, including serum uric acid, creatinine, and urea nitrogen in UUO mice. Inflammatory cytokines, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and interleukin (IL)-1β, but not IL-6, were down-regulated by emodin administration. Emodin decreased the expression levels of TGF-β1 and fibrotic-related proteins, including alpha-smooth muscle actin, Collagen IV, and Fibronectin, and increased the expression of E-cadherin. Furthermore, miR-490-3p was decreased in UUO mice and negatively correlated with increased expression of high migration protein A2 (HMGA2). We further confirmed HMGA2 was the target of miR-490-3p. Transfection of miR-490-3p mimics decreased, while transfection of miR-490-3p inhibitors increased fibrotic-related proteins and HMGA2 expression levels in TGF-β1-induced NRK-52E cells. Furthermore, transfection of miR-490-3p mimics enhanced the anti-fibrotic effects of emodin, while transfection of miR-490-3p inhibitors abolished the protective effects of emodin. Thus, as a novel target of emodin that prevents renal fibrosis in the HMGA2-dependent signaling pathway, miR-490-3p has potential implications in CKD pathology.Copyright © 2023 Wang, Wang, Li, Zhou, Wang, Long, Wang, Li, Huang and Ba.