Exosomal miR-211 contributes to pulmonary hypertension via attenuating CaMK1/PPAR-gamma axis

doi:10.1016/j.vph.2020.106820

科研成果详情

题名	Exosomal miR-211 contributes to pulmonary hypertension via attenuating CaMK1/PPAR-gamma axis
作者	Zhang, Shuhao 1; Liu, Jiantao 2; Zheng, Kaidi3; Chen, Luowei 1; Sun, Yupeng 1; Yao, Zhengze 1; Sun, Yiruo 2; Lin, Yufan 1; Lin, Kexin 2; Yuan, Linbo4
发表日期	2021-02
发表期刊	VASCULAR PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Pulmonary hypertension miR-211 CaMK1 PPAR-gamma Exosome
摘要	Aim: Exsomes play a significant role in increasing pathophysiological processes by delivering their content. Recently, a variety of studies have showed exosomal microRNAs (miRNAs) are involved in pulmonary hyper tension (PH) notably. In this study, we found that exosomal miR-211 was overexpressed in hypoxia-induced PH rats but its intrinsic regulation was unclear. Therefore, our aim was to reveal the underlying mechanism which overexpressed exosomal miR-211 targeted in the development of PH. Methods: 18 male SD rats were randomly divided into normoxia and hypoxia group, housed in normal or hypoxic chamber for 3 weeks respectively. Then, mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance(PVR), right ventricular hypertrophy index(RV/(LV + S)), the percentage of medial wall area (WA%) and the percentage of medial wall thickness (WT%) were measured. Expression of miR-211 in exosomes was detected by qRT-PCR. Expression of Ca2+/calmodulin-dependent kinase1(CaMK1)and peroxisome proliferator-activated receptors-gamma(PPAR-gamma)in lung tissue were detected by Western blot(WB); After miR-211 overexpressed exosomes were injected to rats through caudal vein, mPAP, PVR, RV/(LV + S), WA% and WT% were also measured. Sequentially, hypoxia rats were injected with lentivirus riched in miR-211 inhibitor via tail vein, and PH-related indicators were measured. In vitro, after miR-211 was positively or negatively regulated in pulmonary arterial smooth muscle cell (PASMC) by plasmid transfection, proliferation of PASMC was detected by CCK8, as well as the expression of CaMK1 and PPAR gamma. Further, the relationship between CaMK1 and miR-211 was verified by Dual-Luciferase assay. And the regulatory relationship of CaMK1/PPAR gamma aixs was demonstrated in PASMC. Results: Evident increases of mPAP, PVR, RVHI, WT% and WA% were observed with hypoxia administration. And the concentration of plasma exosomes in hypoxia rats was increased and positively correlated with the above indexes. miR-211 in exosomes of PH was upregulated while the expression of CaMK1 and PPAR-gamma decreased in lung tissues. Further, injection of exosomes overexpressed with miR-211 demonstrated that exosomal miR-211 aggravated PH while inhibition of miR-211 attenuated PH in rats. In vitro, overexpression of miR-211 promoted the proliferation of PASMC and inhibited expression of CaMK1 and PPAR-gamma in PASMC. And Dual-luciferase assay demonstrated that CaMK1 was a downstream gene of miR-211. Plasmid transfection experiments indicated that CaMK1 can promote PPAR-gamma expression. Conclusion: Exosomal miR-211 promoted PH via inhibiting CaMK1/PPAR-gamma axis, promoting PASMC proliferation in rats.
资助项目	Science and Technology Plan Project of Wenzhou [Y20190053]; Research Development Foundation of Wenzhou Medical University [QTJ19021]; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission [2021KY778]; Research Project of students in Wenzhou Medical University [wyx2019101065, wyx2018101116]; Science and Technology Innovation Plan and Xin-miao Talents of Zhejiang Province [2019R413017, 2020R413026]; National College Student Innovation and Entrepreneurship Training Program [201910343013]; National Natural Science Foundations of ChinaNational Natural Science Foundation of China (NSFC) [81701620]
出版者	ELSEVIER SCIENCE INC
出版地	NEW YORK
ISSN	1537-1891
EISSN	1879-3649
卷号	136 页码:106820
DOI	10.1016/j.vph.2020.106820
页数	12
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000613540200006
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33238205
SCOPUSEID	2-s2.0-85097889245
通讯作者地址	[Yuan, Linbo]Department of Physiology,Basic Medical Science School,Wenzhou Medical University,Wenzhou,China
Scopus学科分类	Physiology;Molecular Medicine;Pharmacology
引用统计	被引频次：6[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/13610
专题	第一临床医学院（信息与工程学院）、附属第一医院附属第二医院第二临床医学院、附属第二医院、育英儿童医院基础医学院（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）_生物科学系_生物化学与分子生物学
通讯作者	Yuan, Linbo
作者单位	1.School of First Clinical Medicine,Wenzhou Medical University,Wenzhou,China; 2.School of Second Clinical Medicine,Wenzhou Medical University,Wenzhou,China; 3.Department of Biochemistry,Basic Medical Science School,Wenzhou Medical University,Wenzhou,China; 4.Department of Physiology,Basic Medical Science School,Wenzhou Medical University,Wenzhou,China
第一作者单位	温州医科大学
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	温州医科大学
推荐引用方式 GB/T 7714	Zhang, Shuhao,Liu, Jiantao,Zheng, Kaidi,et al. Exosomal miR-211 contributes to pulmonary hypertension via attenuating CaMK1/PPAR-gamma axis[J]. VASCULAR PHARMACOLOGY,2021,136:106820.
APA	Zhang, Shuhao., Liu, Jiantao., Zheng, Kaidi., Chen, Luowei., Sun, Yupeng., ... & Yuan, Linbo. (2021). Exosomal miR-211 contributes to pulmonary hypertension via attenuating CaMK1/PPAR-gamma axis. VASCULAR PHARMACOLOGY, 136, 106820.
MLA	Zhang, Shuhao,et al."Exosomal miR-211 contributes to pulmonary hypertension via attenuating CaMK1/PPAR-gamma axis".VASCULAR PHARMACOLOGY 136(2021):106820.