菊醇介导的 trx-1 激活可通过抑制 JNK/Cx43 信号通路减轻肾脏纤维化。

IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY Renal Failure Pub Date : 2024-12-01 Epub Date: 2024-09-05 DOI:10.1080/0886022X.2024.2398710
Neng Bao, Jin Wang, Qiyu Yue, Fang Cao, Xuejing Gu, Kejian Wen, Wei Kong, Mingjia Gu
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引用次数: 0

摘要

目的:本研究旨在探讨金丝桃醇对肾脏纤维化的抑制作用及其分子机制:方法:首先通过网络药理学分析预测了金合欢醇的潜在靶点,并利用维恩图和STRING数据库构建了这些靶点的蛋白-蛋白相互作用网络。GO富集分析预测了金丝桃醇治疗肾脏纤维化的生物学过程。随后,分别利用单侧输尿管梗阻(UUO)诱导的CKD小鼠模型和HK-2细胞模型进行了体内和体外实验。在小鼠模型中,给药不同剂量的菊醇,通过生化指标、组织学检查和免疫荧光染色评估其肾脏保护作用。在细胞模型中,利用Western印迹和流式细胞术评估了金丝桃醇对Trx-1/JNK/Cx43通路的调节作用:结果:金丝桃醇能明显改善UUO小鼠模型的肾功能障碍和组织病理学损伤,同时降低血清氧化应激标记物。此外,菊醇还能明显上调肾组织中 Trx-1 的表达,并抑制 JNK/Cx43 信号通路的激活。在细胞水平上,菊醇增强了Trx-1的活性,下调了JNK/Cx43信号通路,从而抑制了TGF-β诱导的氧化应激和细胞凋亡:本研究表明,通过激活 Trx-1,抑制 JNK/Cx43 通路,菊醇对肾脏纤维化有明显的抑制作用。这些发现为可能将金丝桃醇用作肾脏纤维化的治疗药物提供了实验支持。
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Chrysophanol-mediated trx-1 activation attenuates renal fibrosis through inhibition of the JNK/Cx43 signaling pathway.

Purpose: This study aimed to investigate the inhibitory effect of chrysophanol on renal fibrosis and its molecular mechanism.

Methods: Initially, potential targets of chrysophanol were predicted through network pharmacology analysis, and a protein-protein interaction network of these targets was constructed using Venn diagrams and the STRING database. GO enrichment analysis predicted the biological process of chrysophanol in treating renal fibrosis. Subsequently, both in vivo and in vitro experiments were conducted using unilateral ureteral obstruction (UUO) induced CKD mouse model and HK-2 cell model, respectively. In the mouse model, different doses of chrysophanol were administered to assess its renal protective effects through biochemical indicators, histological examination, and immunofluorescence staining. In the cell model, the regulatory effect of chrysophanol on the Trx-1/JNK/Cx43 pathway was evaluated using western blotting and flow cytometry.

Results: Chrysophanol treatment significantly ameliorated renal dysfunction and histopathological damage in the UUO mouse model, accompanied by a reduction in serum oxidative stress markers. Furthermore, chrysophanol markedly upregulated the expression of Trx-1 in renal tissues and inhibited the activation of the JNK/Cx43 signaling pathway. At the cellular level, chrysophanol enhanced the activity of Trx-1 and downregulated the JNK/Cx43 signaling pathway, thereby inhibiting TGF-β induced oxidative stress and cell apoptosis.

Conclusion: This study demonstrated a significant inhibitory effect of chrysophanol on renal fibrosis, mediated by the activation of Trx-1 to inhibit the JNK/Cx43 pathway. These findings provide experimental support for the potential use of chrysophanol as a therapeutic agent for renal fibrosis.

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来源期刊
Renal Failure
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.
期刊最新文献
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