Urantide alleviates atherosclerosis-related liver and kidney injury via the Wnt/β-catenin signaling pathway in ApoE(-/-) mice.

IF 1.1 4区医学 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS Herz Pub Date : 2024-08-01 Epub Date: 2023-11-20 DOI:10.1007/s00059-023-05219-w

Yu-Hang Xu, Jia-Yi Xie, Shen Huang, Tu Wang, Hai-Peng Cui, Juan Zhao

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Abstract

Objective: To investigate the role of urantide in the prevention and treatment of atherosclerosis (AS)-related liver and kidney injury by antagonizing the urotensin II/urotensin receptor (UII/UT) system and regulating the Wnt/β-catenin signaling pathway.

Methods: Atherosclerotic ApoE^-/- mice were treated with 20 mg/kg, 30 mg/kg, and 40 mg/kg urantide for 14 days.

Results: When ApoE^-/- mice developed AS, significant pathological changes occurred in the liver and kidney, and the UII/UT system in tissue was highly activated; furthermore, the Wnt/β-catenin signalling pathway was activated, and proteins related to this signalling pathway, such as GSK-3β, AXIN2, CK‑1, and APC, were significantly downregulated. After urantide treatment, the pathological damage to the liver and kidney was effectively improved, the activity of the UII/UT system was effectively inhibited, and the expression of the Wnt/β-catenin signalling pathway and related proteins was restored. Wnt/β-catenin signals were mainly localized in the cytoplasm, renal tubules, and interstitium.

Conclusion: Urantide could improve AS-related liver and kidney injury by antagonizing the UII/UT system, and the improvements in liver and kidney function in atherosclerotic ApoE^-/- mice may be related to inhibition of the Wnt/β-catenin signalling pathway.

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在ApoE(-/-)小鼠中，Urantide通过Wnt/β-catenin信号通路减轻动脉粥样硬化相关的肝肾损伤。

目的:探讨乌兰提德通过拮抗尿紧张素II/尿紧张素受体(UII/UT)系统及调节Wnt/β-catenin信号通路在动脉粥样硬化(AS)相关肝肾损伤中的防治作用。方法:用20 mg/kg、30 mg/kg和40 mg/kg的乌兰替德治疗动脉粥样硬化ApoE-/-小鼠14天。结果:ApoE-/-小鼠发生AS时，肝、肾发生明显病理改变，组织内UII/UT系统高度激活;Wnt/β-catenin信号通路被激活，与该信号通路相关的GSK-3β、AXIN2、CK - 1、APC等蛋白显著下调。urantide治疗后，肝、肾病理损伤得到有效改善，UII/UT系统活性得到有效抑制，Wnt/β-catenin信号通路及相关蛋白表达恢复。Wnt/β-catenin信号主要定位于细胞质、肾小管和间质。结论:Urantide可通过拮抗UII/UT系统改善as相关肝肾损伤，其对动脉粥样硬化ApoE-/-小鼠肝肾功能的改善可能与抑制Wnt/β-catenin信号通路有关。

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

Herz 医学-心血管系统

CiteScore

3.00

自引率

5.90%

发文量

审稿时长

4-8 weeks

期刊介绍： Herz is the high-level journal for further education for all physicians interested in cardiology. The individual issues of the journal each deal with specific topics and comprise review articles in English and German written by competent and esteemed authors. They provide up-to-date and comprehensive information concerning the speciality dealt with in the issue. Due to the fact that all relevant aspects of the pertinent topic of an issue are considered, an overview of the current status and progress in cardiology is presented. Reviews and original articles round off the spectrum of information provided.