ArticleStem cells (Dayton, Ohio)2014
Low-dose 6-bromoindirubin-3'-oxime induces partial dedifferentiation of endothelial cells to promote increased neovascularization.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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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
16 citing papers in PubMed, 22 citations in OpenAlex.
- Histone variants: key regulators of inflammation in cell dedifferentiation and transdifferentiation.Frontiers in immunology · 2025Review
- Cell-based assay to detect small molecules restoring levels of let-7 miRNAs.American journal of cancer research · 2024Article
- Transfection of Vein Grafts with Early Growth Response Factor-1 Oligodeoxynucleotide Decoy: Effects on Stem-Cell Genes and Toll-like Receptor-Mediated Inflammation.International journal of molecular sciences · 2023Article
- Transit Amplifying Cells (TACs): a still not fully understood cell population.Frontiers in bioengineering and biotechnology · 2023Review
- Mechanosensitive Stem-Cell Genes and Klotho in Atherosclerotic Aortas: Regulating Spatially Deranged Expression Patterns Using Colchicine Regimens.Journal of clinical medicine · 2022Article
- Cardiomyocytes Cellular Phenotypes After Myocardial Infarction.Frontiers in cardiovascular medicine · 2021Review
- Dedifferentiation: inspiration for devising engineering strategies for regenerative medicine.NPJ Regenerative medicine · 2020Review
- Exosomes in the Regulation of Vascular Endothelial Cell Regeneration.Frontiers in cell and developmental biology · 2019Review
- Competing Endogenous RNA and Coexpression Network Analysis for Identification of Potential Biomarkers and Therapeutics in association with Metastasis Risk and Progression of Prostate Cancer.Oxidative medicine and cellular longevity · 2019Article
- WNT Signaling in Cardiac and Vascular Disease.Pharmacological reviews · 2018Review
- The allosteric glycogen synthase kinase-3 inhibitor NP12 limits myocardial remodeling and promotes angiogenesis in an acute myocardial infarction model.The Journal of biological chemistry · 2017Article
- Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling.Bone research · 2017Article
- Chromatin-modifying agents convert fibroblasts to OCT4+ and VEGFR-2+ capillary tube-forming cells.PloS one · 2017Article
- Epigenetic memory gained by priming with osteogenic induction medium improves osteogenesis and other properties of mesenchymal stem cells.Scientific reports · 2015Article
- Microvascular lesions by estrogen-induced ID3: its implications in cerebral and cardiorenal vascular disease.Journal of molecular neuroscience : MN · 2015Article
- Sustained co-delivery of BIO and IGF-1 by a novel hybrid hydrogel system to stimulate endogenous cardiac repair in myocardial infarcted rat hearts.International journal of nanomedicine · 2015Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Endothelial cell (EC) dedifferentiation in relation to neovascularization is a poorly understood process. In this report, we addressed the role of Wnt signaling in the mechanisms of neovascularization in adult tissues. Here, we show that a low-dose of 6-bromoindirubin-3'-oxime (BIO), a competitive inhibitor of glycogen synthase kinase-3β, induced the stabilization of β-catenin and its subsequent direct interaction with the transcription factor NANOG in the nucleus of ECs. This event induced loss of VE-cadherin from the adherens junctions, increased EC proliferation accompanied by asymmetric cell division (ACD), and formed cellular aggregates in hanging drop assays indicating the acquisition of a dedifferentiated state. In a chromatin immunoprecipitation assay, nuclear NANOG protein bound to the NANOG- and VEGFR2-promoters in ECs, and the addition of BIO activated the NANOG-promoter-luciferase reporter system in a cell-based assay. Consequently, NANOG-knockdown decreased BIO-induced NOTCH-1 expression, thereby decreasing cell proliferation, ACD, and neovascularization. In a Matrigel plug assay, BIO induced increased neovascularization, secondary to the presence of vascular endothelial growth factor (VEGF). Moreover, in a mouse model of hind limb ischemia, BIO augmented neovascularization that was coupled with increased expression of NOTCH-1 in ECs and increased smooth muscle α-actin(+) cell recruitment around the neovessels. Thus, these results demonstrate the ability of a low-dose of BIO to augment neovascularization secondary to VEGF, a process that was accompanied by a partial dedifferentiation of ECs via β-catenin and the NANOG signaling 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 OpenQuestion graph.