Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages

doi:10.3389/fphar.2021.639558

科研成果详情

题名	Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages
作者	Lu, Lin 1; Huang, Jianjian2; Xue, Xia 1; Wang, Ting 1; Huang, Zhouqing1; Li, Jianmin3
发表日期	2021-04-20
发表期刊	FRONTIERS IN PHARMACOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	berberine EMMPRIN (extracellular matrix metalloproteinase inducer) MMP-9 oxLDL
其他关键词	MATRIX METALLOPROTEINASE INDUCER ; THERAPEUTIC TARGET ; P2X(7) RECEPTOR ; CELLS ; ACTIVATION ; INJURY ; GENE ; ATHEROSCLEROSIS ; PATHWAY ; DIET
摘要	Elevated extracellular matrix metalloproteinase inducer (EMMPRIN) and matrix metalloproteinase-9 (MMP-9) in oxidized low density lipoprotein (oxLDL)-induced macrophages leads to the progression of vulnerable plaques by degradation of the extracellular matrix. Our previous report showed that berberine regulates the expression of both EMMPRIN and MMP-9. In addition, P2X7 receptor (P2X7R) upregulation plays a crucial role in the development of atherosclerosis. However, it is unclear whether berberine regulated P2X7R level to inhibit both EMMPRIN and MMP-9 expession in macrophages. In the present study, we investigated the impact of berberine on P2X7R expression and the regulation of P2X7R in the expression of EMMPRIN and MMP-9 in oxLDL-induced macrophages. We found that P2X7R expression was increased, miR150-5p was reduced in oxLDL-induced macrophages, relatively. And A-438079 (a P2X7R inhibitor) or miR150-5p mimic treatment greatly reversed the upregulation of EMMPRIN and MMP-9 expression. Moreover, A-438079 significantly reduced oxLDL-induced AMP-activated protein kinase-alpha (AMPK-alpha) phosphorylation and reversed the activation of mitogen-activated protein kinase (MAPK), which in turn decreased the expression of EMMPRIN and MMP-9. These findings illustrate that P2X7R suppresses EMMPRIN and MMP-9 expression by inhibiting the AMPK-alpha/MAPK pathway in oxLDL-induced macrophages. Accordingly, exposure to berberine markedly upregulated miR150-5p, decreased P2X7R expression and downregulated MMP-9 and EMMPRIN levels in oxLDL-induced macrophages, resulting in AMPK-alpha/MAPK (JNK, p38, and ERK) inactivation. Overall, these results indicate that berberine increased miR150-5p level, subsequently inhibits P2X7R-mediated EMMPRIN and MMP-9 expression by suppressing AMPK-alpha and MAPK signaling in oxLDL-induced macrophages.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81670227, 82070446]; Wenzhou Science and Technology Bureau [Y20180099, Y2020242]; key specialty of traditional Chinese Medicine of Zhejiang Provincial in the 13th Five-Year Plan period (Emergency Department)
出版者	FRONTIERS MEDIA SA
出版地	LAUSANNE
ISSN	1663-9812
卷号	12 页码:639558
DOI	10.3389/fphar.2021.639558
页数	10
WOS类目	Pharmacology & Pharmacy
WOS研究方向	Pharmacology & Pharmacy
WOS记录号	WOS:000646601500001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	33959010
PMC记录号	PMC8093865
SCOPUSEID	2-s2.0-85105246729
通讯作者地址	[Huang, Zhouqing]The Key Laboratory of Cardiovascular Disease of Wenzhou,Department of Cardiology,The First Affiliated Hospital of WenZhou Medical University,Wenzhou,China ; [Huang, Jianjian]Department of Anesthesiology,Wenzhou Medical University,Wenzhou,China ; [Li, Jianmin]Department of Pathology,The First Affiliated Hospital of WenZhou Medical University,Wenzhou,China
Scopus学科分类	Pharmacology;Pharmacology (medical)
引用统计	被引频次：8[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/14099
专题	附属第一医院第一临床医学院（信息与工程学院）、附属第一医院_麻醉科
通讯作者	Huang, Jianjian; Huang, Zhouqing; Li, Jianmin
作者单位	1.The Key Laboratory of Cardiovascular Disease of Wenzhou,Department of Cardiology,The First Affiliated Hospital of WenZhou Medical University,Wenzhou,China; 2.Department of Anesthesiology,Wenzhou Medical University,Wenzhou,China; 3.Department of Pathology,The First Affiliated Hospital of WenZhou Medical University,Wenzhou,China
第一作者单位	附属第一医院; 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	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院; 麻醉科
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Lu, Lin,Huang, Jianjian,Xue, Xia,et al. Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages[J]. FRONTIERS IN PHARMACOLOGY,2021,12:639558.
APA	Lu, Lin, Huang, Jianjian, Xue, Xia, Wang, Ting, Huang, Zhouqing, & Li, Jianmin. (2021). Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages. FRONTIERS IN PHARMACOLOGY, 12, 639558.
MLA	Lu, Lin,et al."Berberine Regulated miR150-5p to Inhibit P2X7 Receptor, EMMPRIN and MMP-9 Expression in oxLDL Induced Macrophages".FRONTIERS IN PHARMACOLOGY 12(2021):639558.