ArticlePloS one2016
The Angiogenic Effect of microRNA-21 Targeting TIMP3 through the Regulation of MMP2 and MMP9.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 92 citations in OpenAlex.
- Elucidating the Anticancer Mechanisms of Tetrahydroxycurcumin: A Comprehensive Review of Preclinical Studies.Food science & nutrition · 2025Review
- MicroRNA-21a-5p Promotes Cerebral Angiogenesis in Transient Ischemic Attack by Targeting RBMS3 and Subsequently Modulating the TGFBR1/SMAD2/3 Pathway.CNS neuroscience & therapeutics · 2025Article
- Extracellular Matrix (ECM) Aging in the Retina: The Role of Matrix Metalloproteinases (MMPs) in Bruch's Membrane Pathology and Age-Related Macular Degeneration (AMD).Biomolecules · 2025Review
- Novel therapeutic target for diabetic kidney disease through downregulation of miRNA-192-5p and miRNA-21-5p by celastrol: implication of autophagy, oxidative stress, and fibrosis.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Critical roles of miR-21 in promotions angiogenesis: friend or foe?Clinical and experimental medicine · 2025Review
- Simultaneous effect of miR-21 suppression and miR-143 restoration on inhibition of proliferation and migration in SW-480 colorectal cancer cells.BioImpacts : BI · 2025Article
- Statistical analysis supports pervasive RNA subcellular localization and alternative 3' UTR regulation.eLife · 2024Article
- Current status and new directions for hepatocellular carcinoma diagnosis.Liver research (Beijing, China) · 2024Review
- Tissue Inhibitor of Metalloproteinase 3: Unravelling Its Biological Function and Significance in Oncology.International journal of molecular sciences · 2024Review
- Simultaneous suppression of miR-21 and restoration of miR-145 in gastric cancer cells; a promising strategy for inhibition of cell proliferation and migration.BioImpacts : BI · 2024Article
- Upregulated MicroRNA-21 Drives the Proliferation of Lymphatic Malformation Endothelial Cells by Inhibiting PDCD4.The Journal of investigative dermatology · 2023Article
- Exosomal microRNAs and long noncoding RNAs: as novel biomarkers for endometriosis.Cell and tissue research · 2023Review
- An Overview of the Role of MicroRNAs on Carcinogenesis: A Focus on Cell Cycle, Angiogenesis and Metastasis.International journal of molecular sciences · 2023Review
- Isolation and characterization of ZK002, a novel dual function snake venom protein fromFrontiers in pharmacology · 2023Article
- Cancer-derived exosomal miR-197-3p confers angiogenesis via targeting TIMP2/3 in lung adenocarcinoma metastasis.Cell death & disease · 2022Article
- Targeting miR-21 in spinal cord injuries: a game-changer?Molecular medicine (Cambridge, Mass.) · 2022Review
- AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation.International journal of molecular sciences · 2021Article
- miR-21 mimic blocks obesity in mice: A novel therapeutic option.Molecular therapy. Nucleic acids · 2021Article
- An Insight into the microRNAs Associated with Arteriovenous and Cavernous Malformations of the Brain.Cells · 2021Review
- Knockdown of long non-coding RNA RMRP protects cerebral ischemia-reperfusion injury via the microRNA-613/ATG3 axis and the JAK2/STAT3 pathway.The Kaohsiung journal of medical sciences · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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