Role of TGF-β1/Smad3 signalling pathway in renal tubulointerstitial fibrosis and renal damage in elderly rats with isolated systolic hypertension induced by increased pulse pressure.

IF 2.1 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Acta cardiologica Pub Date : 2025-04-01 Epub Date: 2025-01-09 DOI:10.1080/00015385.2024.2445339

Lu Li, Guiling Xia, Lei Lei, Qiong Hu, Xueying Wei, Mengbi Cui, Qiaoling Tang, Donghua Yang, Anju Zhao

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引用次数: 0

Abstract

Objective: Elevated systolic blood pressure and increased pulse pressure are closely associated with renal damage; however, the exact mechanism remains unclear. Therefore, we investigated the effects of increased pulse pressure on tubulointerstitial fibrosis and renal damage in elderly rats with isolated systolic hypertension (ISH). Additionally, the role of renal tubular epithelial-mesenchymal transition (EMT) and its upstream signalling pathways were elucidated.

Methods: Ten-month-old male rats were randomly divided into control and ISH groups, with seven rats in each group administered warfarin and vitamin K1 for 6 weeks. Blood pressure, renal function, mean blood flow in the common iliac artery, and diastolic vessel diameter were assessed, and the rat kidney medulla was collected for histological, genetic, and protein level analysis.

Results: Increased pulse pressure, abnormal renal function, and increased shear stress were detected in rats with ISH. Histology assessments revealed fibrosis in the interstitium of ISH rats. Epithelial marker E-cadherin protein expression was decreased, while the protein expression of interstitial markers α-SMA and Vimentin was increased, and transforming growth factor (TGF)-β1/Smad3 signalling was upregulated in the kidney tissue of ISH rats.

Conclusions: Increased pulse pressure in elderly rats with ISH caused an increase in shear stress. These effects led to the development of EMT and the activation of its upstream TGF-β1/Smad3 signalling pathway, ultimately leading to renal tubular interstitial fibrosis causing renal injury.

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TGF-β1/Smad3信号通路在脉压升高引起的老年孤立性收缩期高血压大鼠肾小管间质纤维化和肾损害中的作用

目的：收缩压升高和脉压升高与肾损害密切相关；然而，确切的机制尚不清楚。因此，我们研究了脉压升高对老年孤立性收缩期高血压（ISH）大鼠小管间质纤维化和肾损害的影响。此外，我们还阐明了肾小管上皮-间质转化（EMT）及其上游信号通路的作用。方法：将10月龄雄性大鼠随机分为对照组和ISH组，每组7只大鼠分别给予华法林和维生素K1治疗6周。评估血压、肾功能、髂总动脉平均血流量和舒张血管直径，收集大鼠肾髓质进行组织学、遗传和蛋白水平分析。结果：ISH大鼠脉压增高，肾功能异常，切应力增高。组织学检查显示ISH大鼠间质纤维化。ISH大鼠肾组织上皮标志物E-cadherin蛋白表达降低，间质标志物α-SMA和Vimentin蛋白表达升高，转化生长因子(TGF)-β1/Smad3信号表达上调。结论：老年ISH大鼠脉压增高可引起切变应力增高。这些作用导致EMT发生并激活其上游TGF-β1/Smad3信号通路，最终导致肾小管间质纤维化，造成肾损伤。

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来源期刊

Acta cardiologica 医学-心血管系统

CiteScore

2.50

自引率

12.50%

发文量

115

审稿时长

2 months

期刊介绍： Acta Cardiologica is an international journal. It publishes bi-monthly original, peer-reviewed articles on all aspects of cardiovascular disease including observational studies, clinical trials, experimental investigations with clear clinical relevance and tutorials.