wtap介导的m6A对BASP1 mRNA的修饰有助于AAA的铁下垂。

IF 1.1 4区 医学 Q4 CARDIAC & CARDIOVASCULAR SYSTEMS
Zexiang Tian, Wei Li, Jian Wang, Shuzhen Li
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引用次数: 0

摘要

背景:腹主动脉瘤(AAA)是一种常见的动脉瘤,常与动脉粥样硬化相关,可导致动脉破裂和死亡。脑丰富膜附着信号蛋白1 (BASP1)与多种病理生理过程有关,但其在AAA中的作用尚未见报道。方法:采用实时定量聚合酶链反应(qRT-PCR)和western blot检测BASP1和Wilms' tumor 1-associated protein (WTAP)的表达。采用血管紧张素- ii (Ang-II)体外诱导AAA模型,探讨BASP1在AAA中的作用及机制,分别采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基溴化四氮唑(MTT)、流式细胞术及各种试剂盒检测细胞活力、凋亡、氧化应激水平和Fe2+水平。在机制方面,利用甲基化RNA免疫沉淀(MeRIP)-qPCR、双荧光素酶报告基因实验和细胞色素实验来评估BASP1与WTAP的关系。结果:AAA患者主动脉组织中高表达BASP1, Ang-II可通过治疗血管平滑肌细胞(VSMCs)诱导AAA模型。在细胞功能方面,BASP1敲低会损害AAA和Ang-II引起的铁下垂。在机械上,WTAP介导了n6 -甲基腺苷(m6A)修饰和BASP1 mRNA的稳定性。同时,WTAP在患者AAA组织中高表达,上调BASP1可减弱WTAP沉默对AAA和铁下垂的影响。结论:WTAP通过调节BASP1的m6A水平,促进VSMCs细胞活力,抑制Ang-II诱导的凋亡和铁凋亡。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
WTAP-mediated m6A modification on BASP1 mRNA contributes to ferroptosis in AAA.

Background: Abdominal aortic aneurysm (AAA) is a common aneurysm that is often associated with atherosclerosis and can lead to artery rupture and death. Brain abundant membrane attached signal protein 1 (BASP1) is related to a variety of pathophysiological processes, but its role in AAA has not been reported.

Methods: Real-time quantitative polymerase chain reaction (qRT-PCR) and western blot were used to detect the expressions of BASP1 and Wilms' tumor 1-associated protein (WTAP). Angiotensin-II (Ang-II) was employed for inducing AAA models in vitro to explore the effects and mechanism of BASP1 in AAA. Cell viability, apoptosis, oxidative stress level, and Fe2+ level were measured by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometry, and various kits, respectively. In terms of mechanism, the methylated RNA immunoprecipitation (MeRIP)-qPCR, the dual luciferase reporter assay, and the cytochrome experiments were utilized to evaluate the relationship between BASP1 and WTAP.

Results: A highly expressed level of BASP1 was observed in aortic tissues of AAA patients and Ang-II could induce AAA models by treating vascular smooth muscle cells (VSMCs). In cellular function, BASP1 knockdown impaired AAA and ferroptosis resulted from Ang-II. Mechanically, WTAP mediated the N6-methyladenosine (m6A) modification and mRNA stability of BASP1. Meanwhile, WTAP was highly expressed in AAA tissues of patients and the effects of WTAP silence in AAA and ferroptosis were diminished by up-regulated BASP1.

Conclusion: WTAP promotes cell viability and inhibits apoptosis and ferroptosis resulted from Ang-II in VSMCs by mediating the m6A level of BASP1.

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来源期刊
General Thoracic and Cardiovascular Surgery
General Thoracic and Cardiovascular Surgery Medicine-Pulmonary and Respiratory Medicine
CiteScore
2.70
自引率
8.30%
发文量
142
期刊介绍: The General Thoracic and Cardiovascular Surgery is the official publication of The Japanese Association for Thoracic Surgery and The Japanese Association for Chest Surgery, the affiliated journal of The Japanese Society for Cardiovascular Surgery, that publishes clinical and experimental studies in fields related to thoracic and cardiovascular surgery.
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