Curcumin alleviates renal fibrosis in chronic kidney disease by targeting the circ_0008925-related pathway.

IF 3 3区医学 Q1 UROLOGY & NEPHROLOGY

Renal Failure Pub Date : 2025-12-01 Epub Date: 2025-03-04 DOI:10.1080/0886022X.2024.2444393

Peng An, Xingyao Li, Yanhong Zhao, Liuyun Li, Yafeng Wang, Wenfang Wang, Tao Zhang, Sicen Wang, Xili Wu

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Abstract

Background: Curcumin has been shown to inhibit renal fibrosis, but whether curcumin mediates renal fibrosis progression by regulating the circular RNA (circRNA)-related pathway remain unclear.

Methods: TGF-β1 was used to construct renal injury and fibrosis cell model. Cell growth was evaluated by cell counting kit 8 assay, EdU assay and flow cytometry. Fibrosis marker and interleukin 6 signal transducer (IL6ST) protein levels were measured using western bolt analysis. Inflammation factor concentrations were determined by ELISA. Circ_0008925, miR-204-5p and IL6ST expression was assessed by qRT-PCR. Unilateral ureteral obstruction (UUO) mice models were constructed to assess the role of curcumin in vivo.

Results: Curcumin treatment alleviated TGF-β1-induced HK-2 cell apoptosis, inflammation and fibrosis in vitro, as well as relieved renal injury in UUO mice models in vivo. Circ_0008925 was highly expressed in TGF-β1-induced HK-2 cells and its expression was inhibited by curcumin. Circ_0008925 could sponge miR-204-5p to positively regulate IL6ST. The inhibition effect of curcumin on TGF-β1-induced HK-2 cell injury and fibrosis was reversed by circ_0008925 overexpression, miR-204-5p inhibitor or IL6ST upregulation. Besides, circ_0008925 knockdown inhibited TGF-β1-induced HK-2 cell injury and fibrosis by suppressing IL6ST expression.

Conclusion: Curcumin relieved renal fibrosis through regulating circ_0008925/miR-204-5p/IL6ST axis.

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姜黄素通过靶向circ_0008925相关通路缓解慢性肾病肾纤维化。

背景：姜黄素已被证明可抑制肾纤维化，但姜黄素是否通过调节环状RNA （circRNA）相关途径介导肾纤维化进展尚不清楚。方法：采用TGF-β1构建肾损伤及纤维化细胞模型。采用细胞计数试剂盒8、EdU、流式细胞术检测细胞生长情况。采用western bolt法检测纤维化标志物和白细胞介素6信号传感器（IL6ST）蛋白水平。ELISA法测定各组炎症因子浓度。采用qRT-PCR检测Circ_0008925、miR-204-5p和IL6ST的表达。建立单侧输尿管梗阻（UUO）小鼠模型，在体内评价姜黄素的作用。结果：姜黄素在体外可减轻TGF-β1诱导的HK-2细胞凋亡、炎症和纤维化，在体内可减轻UUO小鼠模型肾损伤。Circ_0008925在TGF-β1诱导的HK-2细胞中高表达，姜黄素抑制其表达。Circ_0008925可以海绵miR-204-5p正向调节IL6ST。姜黄素对TGF-β1诱导的HK-2细胞损伤和纤维化的抑制作用被circ_0008925过表达、miR-204-5p抑制剂或IL6ST上调逆转。此外，circ_0008925敲低可通过抑制IL6ST表达抑制TGF-β1诱导的HK-2细胞损伤和纤维化。结论：姜黄素通过调节circ_0008925/miR-204-5p/IL6ST轴减轻肾纤维化。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Renal Failure 医学-泌尿学与肾脏学

CiteScore

3.90

自引率

13.30%

发文量

374

审稿时长

1 months

期刊介绍： Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.