Kurarinone protects against renal injury and fibrosis after unilateral ureteral obstruction through enhancement of the Nrf-2 signaling pathway

IF 2.2 4区生物学 Q3 CELL BIOLOGY

Journal of Molecular Histology Pub Date : 2025-08-29 DOI:10.1007/s10735-025-10578-1

Tiancao Dong, Dongyang Zhao, Sen Jiang, Yi Gu, Chunxue Wang, Qian Yang, Tong Liu, Xiandong Liu

{"title":"Kurarinone protects against renal injury and fibrosis after unilateral ureteral obstruction through enhancement of the Nrf-2 signaling pathway","authors":"Tiancao Dong, Dongyang Zhao, Sen Jiang, Yi Gu, Chunxue Wang, Qian Yang, Tong Liu, Xiandong Liu","doi":"10.1007/s10735-025-10578-1","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Chronic kidney disease (CKD) is an epidemic with higher cardiovascular risk, and this pathology involves renal injury and fibrosis. Kurarinone (KAR) has anti-inflammatory and anticancer effects, which can regulate immune responses and macrophage polarization. This study aimed to investigate the effect of KAR on model-induced unilateral ureteral obstruction (UUO) renal injury and fibrosis.</p><h3>Methods</h3><p>We constructed the rat model of sham, UUO, UUO + low (10 IU/kg), medium (20 IU/kg) and high (40 IU/kg) doses of KAR groups in vivo, and we analyzed pathologic changes and expression of vimentin and α-smooth muscle actin (α-SMA), cluster of differentiation group 206, F4/80, FN, Snail1, Kim1, small mother against decapentaplegic (Smad) 3 and transforming growth factor-beta [TGF-β1]. Furthermore, we developed the HK-2 cell fibrosis model using TGF-β1 (5 ng/ml) for 24 h in vitro. We used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry to detect α-SMA protein, TGF-β1, Smad3, and p-Smad3 levels in renal tissues. We examine protein levels of the Keap1/Nrf2 pathway using the Nrf-2 inhibitor, ML385, and downregulation of Nrf-2 expression using Western blotting.</p><h3>Results</h3><p>Our results revealed that KAR improved renal function and downregulated α-SMA protein. Furthermore, KAR induced the polarization of M2 macrophages. KAR improved fibrosis by inhibiting the TGF-β1/Smad3 pathway. KAR inhibited renal fibrosis and inflammation by activating the Keap1/Nrf2 pathway in vivo and in vitro.</p><h3>Conclusions</h3><p>KAR inhibited renal fibrosis and inflammation through the Keap1/Nrf-2 pathway, indicating that it may become a small molecular drug for chronic kidney disease.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2000,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-025-10578-1.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Histology","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10735-025-10578-1","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Chronic kidney disease (CKD) is an epidemic with higher cardiovascular risk, and this pathology involves renal injury and fibrosis. Kurarinone (KAR) has anti-inflammatory and anticancer effects, which can regulate immune responses and macrophage polarization. This study aimed to investigate the effect of KAR on model-induced unilateral ureteral obstruction (UUO) renal injury and fibrosis.

Methods

We constructed the rat model of sham, UUO, UUO + low (10 IU/kg), medium (20 IU/kg) and high (40 IU/kg) doses of KAR groups in vivo, and we analyzed pathologic changes and expression of vimentin and α-smooth muscle actin (α-SMA), cluster of differentiation group 206, F4/80, FN, Snail1, Kim1, small mother against decapentaplegic (Smad) 3 and transforming growth factor-beta [TGF-β1]. Furthermore, we developed the HK-2 cell fibrosis model using TGF-β1 (5 ng/ml) for 24 h in vitro. We used real-time quantitative polymerase chain reaction, Western blotting, and immunohistochemistry to detect α-SMA protein, TGF-β1, Smad3, and p-Smad3 levels in renal tissues. We examine protein levels of the Keap1/Nrf2 pathway using the Nrf-2 inhibitor, ML385, and downregulation of Nrf-2 expression using Western blotting.

Results

Our results revealed that KAR improved renal function and downregulated α-SMA protein. Furthermore, KAR induced the polarization of M2 macrophages. KAR improved fibrosis by inhibiting the TGF-β1/Smad3 pathway. KAR inhibited renal fibrosis and inflammation by activating the Keap1/Nrf2 pathway in vivo and in vitro.

Conclusions

KAR inhibited renal fibrosis and inflammation through the Keap1/Nrf-2 pathway, indicating that it may become a small molecular drug for chronic kidney disease.

查看原文本刊更多论文

Kurarinone通过增强Nrf-2信号通路保护单侧输尿管梗阻后的肾损伤和纤维化

慢性肾脏疾病（CKD）是一种具有较高心血管风险的流行病，其病理包括肾脏损伤和纤维化。Kurarinone （KAR）具有抗炎和抗癌作用，可调节免疫应答和巨噬细胞极化。本研究旨在探讨KAR对模型性单侧输尿管梗阻（UUO）肾损伤及纤维化的影响。方法构建假、UUO、UUO +低（10 IU/kg）、中（20 IU/kg）、高（40 IU/kg）剂量KAR组大鼠体内模型，分析vimentin、α-平滑肌肌动蛋白（α-SMA）、分化组206、F4/80、FN、Snail1、Kim1、小母抗十肢瘫痪（Smad） 3、转化生长因子-β [TGF-β1]的病理变化及表达。此外，我们用TGF-β1 （5 ng/ml）体外培养24 h的HK-2细胞纤维化模型。采用实时定量聚合酶链反应、Western blotting、免疫组织化学检测肾组织中α-SMA蛋白、TGF-β1、Smad3、p-Smad3水平。我们使用Nrf-2抑制剂ML385检测Keap1/Nrf2通路的蛋白水平，并使用Western blotting检测Nrf-2表达的下调。结果KAR可改善肾功能，下调α-SMA蛋白表达。此外，KAR诱导M2巨噬细胞极化。KAR通过抑制TGF-β1/Smad3通路改善纤维化。在体内和体外实验中，KAR通过激活Keap1/Nrf2通路抑制肾脏纤维化和炎症。结论skar通过Keap1/Nrf-2途径抑制肾脏纤维化和炎症，可能成为治疗慢性肾脏疾病的小分子药物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Molecular Histology 生物-细胞生物学

CiteScore

5.90

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.