The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9

doi:10.1371/journal.pone.0149537

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 分子影像中心（筹）

	The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9
	Hu, Jianzhong 2; Ni, Shuangfei 2; Cao, Yong 2; Zhang, Tao 2; Wu, Tianding 2; Yin, Xianzhen 3; Lang, Ye 2; Lu, Hongbin 1
刊名	PLOS ONE
	2016-02-12
卷号	11 期号:2
ISSN号	1932-6203
DOI	10.1371/journal.pone.0149537
文献子类	Article
英文摘要	microRNAs are a novel set of small, non-protein-coding nucleotide RNAs that negatively regulate the expression of target mRNAs. miRNA-21 is a microRNA that is highly enriched in endothelial cells. miRNA-21 has been shown to be a potential pro-angiogenic factor in some biological systems. Our previous study showed that the expression of miRNA-21 was up-regulated after spinal cord injury. However, the effect of miRNA-21 on angiogenesis in the spinal cord was unclear. In this study, to understand the role of miRNA-21 on injured endothelial cells exclusively, an oxygen and glucose deprivation model of endothelial cells was constructed, and the up-regulation of miRNA-21 was discovered in this model. An increased level of miRNA-21 by mimics promoted the survival, migration and tube formation of endothelial cells, which simultaneously inhibited tissue inhibitor of metalloproteinase-3 (TIMP3) expression and promoted matrix metalloproteinase-2 (MMP2) and matrix metalloproteinase-9 (MMP9) expression and secretion. A decreased level of miRNA-21 by antagomir exerted an opposite effect. As is well known, survival, migration and tube formation of endothelial cells are necessary prerequisites for angiogenesis after injury. TIMP3 was validated as a direct target of miRNA-21 by dual-luciferase reporter assay. Silencing with small interfering RNA against TIMP3 promoted tube formation and increased MMP2 and MMP9 expression at the protein level. In vivo, we found that decreased levels of miRNA-21 inhibited angiogenesis after spinal cord injury in rats using synchrotron radiation micro-computed tomography. In summary, these findings suggest that miRNA-21 has a protective effect on angiogenesis by reducing cell death and promoting cell survival, migration and tube formation via partially targeting the TIMP3 by potentially regulating MMP2 and MMP9. TIMP3 is a functional target gene. Identifying the role of miRNA-21 in the protection of angiogenesis might offer a novel therapeutic target for secondary spinal cord injury, in which angiogenesis is indispensable.
资助项目	National Natural Science Foundation of China[81371956] ; National Natural Science Foundation of China[81171698] ; Specialized Research Fund for the Doctoral Program of Higher Education[20130162110078]
WOS关键词	SPINAL-CORD-INJURY ; TISSUE INHIBITOR ; IN-VIVO ; MATRIX METALLOPROTEINASES ; ENDOTHELIAL-CELLS ; CONTUSION INJURY ; DOWN-REGULATION ; TUMOR-GROWTH ; LUNG-CANCER ; MIR-21
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000370054100163
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276146]
专题	分子影像中心（筹）
通讯作者	Lu, Hongbin
作者单位	1.Cent S Univ, Xiangya Hosp, Res Ctr Sports Med, Dept Sports Med, Changsha 410008, Hunan, Peoples R China 2.Cent S Univ, Xiangya Hosp, Dept Spine Surg, Changsha 410008, Hunan, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Delivery Syst, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Hu, Jianzhong,Ni, Shuangfei,Cao, Yong,et al. The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9[J]. PLOS ONE,2016,11(2).
APA	Hu, Jianzhong.,Ni, Shuangfei.,Cao, Yong.,Zhang, Tao.,Wu, Tianding.,...&Lu, Hongbin.(2016).The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9.PLOS ONE,11(2).
MLA	Hu, Jianzhong,et al."The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9".PLOS ONE 11.2(2016).