miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2

doi:10.1007/s10557-024-07568-y

科研成果详情

题名	miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2
作者	Wang, Boxiang 1; Xu, Yidin 2; Huang, Yilun 3; Shao, Siming2; Xu, Dongshan 1; Zhang, Yiying 3; Pang, Lingxia4; Nan, Zhuofan 2,5; Ye, Qianxi 1,6; Wang, Yang 7; Wang, Wantie7; Jin, Keke7; Yuan, Linbo8
发表日期	2024-04-24
发表期刊	CARDIOVASCULAR DRUGS AND THERAPY 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Pulmonary hypertension miR-210-5p Pulmonary vascular remodeling
其他关键词	CALCIUM
摘要	AimAberrant expression of ATPase sarcoplasmic/endoplasmic retic Ca2+ transporting 2 (ATP2A2) has attracted attention for its pathophysiologic role in pulmonary hypertension (PH). Several miRNAs, including miR-210-5p, have also been reported to be pathogenic factors in PH, but their exact mechanisms remain unknown. This study aimed to elucidate the potential mechanisms of miR-210-5p and ATP2A2 in MCT-induced PH.MethodsEighteen Sprague-Dawley rats were randomly divided into two groups-monoclonal (MCT) group and control group-and then administered MCT (60 mg/kg) and saline, respectively. mPAP, PVR, RVHI, WT%, and WA% were significantly increased in PH rats after 3 weeks, confirming that the modeling of PH rats was successful. Subsequently, we determined the expression of ATP2A2 and miR-210-5p in lung tissues using WB and qRT-PCR methods. We established an in vitro model using BMP4 and TGF-beta 1 treatment of pulmonary artery smooth muscle cells (PASMCs) and examined the expression of ATP2A2 and miR-210-5p using the same method. To further elucidate the regulatory relationship between ATP2A2 and miR-210-5p, we altered the expression level of miR-210-5p and detected the corresponding changes in ATP2A2 levels. In addition, we demonstrated the relationship by dual luciferase experiments. Finally, the effect of silencing ATP2A2 could be confirmed by the level of cell membrane Ca2+ in PAMSCs.ResultsUp-regulation of miR-210-5p and down-regulation of ATP2A2 were observed in the MCT group compared with the control group, which was confirmed in the in vitro model. In addition, elevated miR-210-5p expression decreased the level of ATP2A2 while increasing the proliferation of PASMCs, and the results of the dual luciferase assay further confirmed that ATP2A2 is a downstream target of miR-210-5p. Additionally, silencing ATP2A2 resulted in increased cytoplasmic Ca2+ levels in PAMSCs.ConclusionIn MCT-induced PH, miR-210-5p promotes pulmonary vascular remodeling by inhibiting ATP2A2.
资助项目	Wenzhou Medical University[QTJ19021];Science and Technology Innovation Program for Zhejiang University Students[Wyx2023101055,2023R413047];Science and Technology Plan Project of Wenzhou[Y20210685,2023Y1848];Natural Science Foundation of Zhejiang Province[LGD22H020002];Zhejiang Health Science and Technology Project[2021KY778];
出版者	SPRINGER
ISSN	0920-3206
EISSN	1573-7241
DOI	10.1007/s10557-024-07568-y
页数	9
WOS类目	Cardiac & Cardiovascular Systems ; Pharmacology & Pharmacy
WOS研究方向	Cardiovascular System & Cardiology ; Pharmacology & Pharmacy
WOS记录号	WOS:001207605300001
收录类别	SCIE ; SCOPUS ; PUBMED
在线发表日期	2024-04
URL	查看原文
PubMed ID	38656637
SCOPUSEID	2-s2.0-85191245121
通讯作者地址	[Yuan, Linbo]Department of Physiology,Basic Medical School,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology;Cardiology and Cardiovascular Medicine;Pharmacology (medical)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/212455
专题	第一临床医学院（信息与工程学院）、附属第一医院基础医学院（机能实验教学中心）第二临床医学院、附属第二医院、育英儿童医院阿尔伯塔学院基础医学院（机能实验教学中心）_病理学与病理生理学系基础医学院（机能实验教学中心）_机能学系_生理学
通讯作者	Yuan, Linbo
作者单位	1.The First Clinical Medical College,Wenzhou Medical University,Wenzhou,China; 2.The Second Clinical Medical College,Wenzhou Medical University,Wenzhou,China; 3.Alberta Institute,Wenzhou Medical University,Wenzhou,China; 4.Functionality Experimental Teaching Center,Basic Medical School,Wenzhou Medical University,Wenzhou,China; 5.Department of Urology,Shanghai General Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,China; 6.Department of Cardiovascular Surgery,the First Affiliated Hospital,School of Medicine,Zhejiang University,Zhejiang,China; 7.Department of Pathophysiology,Basic Medical School,Wenzhou Medical University,Wenzhou,China; 8.Department of Physiology,Basic Medical School,Wenzhou Medical University,Wenzhou,China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院
通讯作者单位	病理学与病理生理学系
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院
推荐引用方式 GB/T 7714	Wang, Boxiang,Xu, Yidin,Huang, Yilun,et al. miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2[J]. CARDIOVASCULAR DRUGS AND THERAPY,2024.
APA	Wang, Boxiang., Xu, Yidin., Huang, Yilun., Shao, Siming., Xu, Dongshan., ... & Yuan, Linbo. (2024). miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2. CARDIOVASCULAR DRUGS AND THERAPY.
MLA	Wang, Boxiang,et al."miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2".CARDIOVASCULAR DRUGS AND THERAPY (2024).