ArticleThe Journal of biological chemistry2012
The microRNA miR-199a-5p down-regulation switches on wound angiogenesis by derepressing the v-ets erythroblastosis virus E26 oncogene homolog 1-matrix metalloproteinase-1 pathway.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 79 citations in OpenAlex.
- MicroRNAs expressed during normal wound healing and their associated pathways: A systematic review and bioinformatics analysis.PloS one · 2023Pooled it
- The Wound-Heart Axis: Can Chronic Wounds Contribute to Cardiac Dysfunction?International journal of molecular sciences · 2026Review
- Therapeutic Potential of Modulating Gene-MicroRNA Crosstalk in Burn Injury.International journal of molecular sciences · 2025Review
- Overexpression of miR-199b-5p in Colony Forming Unit-Hill's Colonies Positively Mediates the Inflammatory Response in Subclinical Cardiovascular Disease Model: Metformin Therapy Attenuates Its Expression.International journal of molecular sciences · 2024Article
- miR-199a-5p modulates choroidal neovascularization by regulating Wnt7b/Wnt/β-catenin signaling pathway.Journal of molecular histology · 2024Article
- Role of Angiogenesis and Its Biomarkers in Development of Targeted Tumor Therapies.Stem cells international · 2024Review
- HMSCs exosome-derived miR-199a-5p attenuates sulfur mustard-associated oxidative stress via the CAV1/NRF2 signalling pathway.Journal of cellular and molecular medicine · 2023Article
- Ets1 and IL17RA cooperate to regulate autoimmune responses and skin immunity toFrontiers in immunology · 2023Article
- Neuropilin-1 in the pathogenesis of preeclampsia, HIV-1, and SARS-CoV-2 infection: A review.Virus research · 2022Review
- miR-199-5p regulates spermiogenesis at the posttranscriptional level via targeting Tekt1 in allotriploid crucian carp.Journal of animal science and biotechnology · 2022Article
- Mitochondrial remodelling-a vicious cycle in diabetic complications.Molecular biology reports · 2021Review
- Mesenchymal stem cell as a novel approach to systemic sclerosis; current status and future perspectives.Cell regeneration (London, England) · 2020Review
- Adipose derived mesenchymal stem cell treatment in experimental asherman syndrome induced rats.Molecular biology reports · 2020Article
- Angioregulatory microRNAs in Colorectal Cancer.Cancers · 2019Review
- Overexpression of the Oral Mucosa-Specific microRNA-31 Promotes Skin Wound Closure.International journal of molecular sciences · 2019Article
- Therapeutic strategies for enhancing angiogenesis in wound healing.Advanced drug delivery reviews · 2019Review
- MicroRNA expression profile in retina and choroid in oxygen-induced retinopathy model.PloS one · 2019Article
- MicroRNA 199a and the eNOS (Endothelial NO Synthase)/NO Pathway.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- Exposure of Endothelium to Biomimetic Flow Waveforms Yields Identification of miR-199a-5p as a Potent Regulator of Arteriogenesis.Molecular therapy. Nucleic acids · 2018Article
- Topical Lyophilized Targeted Lipid Nanoparticles in the Restoration of Skin Barrier Function following Burn Wound.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
miR-199a-5p plays a critical role in controlling cardiomyocyte survival. However, its significance in endothelial cell biology remains ambiguous. Here, we report the first evidence that miR-199a-5p negatively regulates angiogenic responses by directly targeting v-ets erythroblastosis virus E26 oncogene homolog 1 (Ets-1). Induction of miR-199a-5p in human dermal microvascular endothelial cells (HMECs) blocked angiogenic response in Matrigel® culture, whereas miR-199a-5p-deprived cells exhibited enhanced angiogenesis in vitro. Bioinformatics prediction and miR target reporter assay recognized Ets-1 as a novel direct target of miR-199a-5p. Delivery of miR-199a-5p blocked Ets-1 expression in HMECs, whereas knockdown endogenous miR-199a-5p induced Ets-1 expression. Matrix metalloproteinase 1 (MMP-1), one of the Ets-1 downstream mediators, was negatively regulated by miR-199a-5p. Overexpression of Ets-1 not only rescued miR-199a-5p-dependent anti-angiogenic effects but also reversed miR-199a-5p-induced loss of MMP-1 expression. Similarly, Ets-1 knockdown blunted angiogenic response and induction of MMP-1 in miR-199a-5p-deprived HMECs. Examination of cutaneous wound dermal tissue revealed a significant down-regulation of miR-199a-5p expression, which was associated with induction of Ets-1 and MMP-1. Mice carrying homozygous deletions in the Ets-1 gene exhibited blunted wound blood flow and reduced abundance of endothelial cells. Impaired wound angiogenesis was associated with compromised wound closure, insufficient granulation tissue formation, and blunted induction of MMP-1. Thus, down-regulation of miR-199a-5p is involved in the induction of wound angiogenesis through derepressing of the Ets-1-MMP1 pathway.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.