ArticleCell death & disease2021
Extracellular vesicles from hypoxia-preconditioned microglia promote angiogenesis and repress apoptosis in stroke mice via the TGF-β/Smad2/3 pathway.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.
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Who cites it
107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 181 citations in OpenAlex.
- Systematic Review of the Differential Effects of TGF-β1 in Ischemic and Hemorrhagic Preclinical Stroke Models.Journal of the American Heart Association · 2025Pooled it
- Association Between Transforming Growth Factor-β1 Polymorphisms and Ischemic Stroke Susceptibility: A Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisPooled it
- An adhesive hydrogel enabling spatiotemporal delivery of umbilical cord exosomes for scarless skin regeneration through immunomodulation and ECM remodeling.Bioactive materials · 2027Article
- Intercellular communication between peripheral monocytes and central nervous system cells in stroke.Neural regeneration research · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Extracellular Vesicles in Cancer: Biomarkers, Mechanisms, and Emerging Diagnostic Technologies.Advanced healthcare materials · 2026Review
- Microglia-Mediated Vascular Network Remodeling After Ischemic Stroke: An Immunovascular Repair Framework.Cells · 2026Review
- Activin A enhances neurofunctional recovery following traumatic spinal cord injury by inhibiting autophagy.Neural regeneration research · 2026Article
- Targeted biohybrid nanoplatform for spinal cord injury treatment: Restoring microglial mitophagy and alleviating oxidative stress.Materials today. Bio · 2026Article
- Extracellular vesicles: Revolutionizing targeted therapy for ischemic stroke.Acta pharmaceutica Sinica. B · 2026Review
- Post-transcriptional activation of TGF-β signaling via SMAD mRNA stabilization by EIF4A3 promotes EMT and metastasis in gastric cancer.Cell biology and toxicology · 2026Article
- CAR Treg therapies for neurodegenerative diseases.iScience · 2026Review
- NFAT1Cellular & molecular biology letters · 2026Article
- Microglial Fkbp5 Impairs Post-Stroke Vascular Integrity and Regeneration by Promoting Yap1-Mediated Glycolysis and Oxidative Phosphorylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neurovascular Unit-Derived Extracellular Vesicles as Regulators of Post-Stroke Pathology and Neurorestoration.Biomolecules · 2026Review
- Extracellular vesicles derived from astrocytes pretreated with melatonin promoted neuro-angiogenesis in mice with ischemic medial prefrontal cortex.Journal of translational medicine · 2026Article
- An integrative clinical and bioinformatic analysis identifies MicroRNAs as biomarkers of ischemic stroke severity.Scientific reports · 2026Article
- Genetic Deletion of Cyclophilin D Results in Enhanced Hypoxia Tolerance in Mice.Cellular and molecular neurobiology · 2026Article
- Article
- Curcumin ameliorates ulcerative colitis via inhibiting STAT3-mediated angiogenesis.Archives of medical science : AMS · 2026Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Systemic transplantation of oxygen-glucose deprivation (OGD)-preconditioned primary microglia enhances neurological recovery in rodent stroke models, albeit the underlying mechanisms have not been sufficiently addressed. Herein, we analyzed whether or not extracellular vesicles (EVs) derived from such microglia are the biological mediators of these observations and which signaling pathways are involved in the process. Exposing bEnd.3 endothelial cells (ECs) and primary cortical neurons to OGD, the impact of EVs from OGD-preconditioned microglia on angiogenesis and neuronal apoptosis by the tube formation assay and TUNEL staining was assessed. Under these conditions, EV treatment stimulated both angiogenesis and tube formation in ECs and repressed neuronal cell injury. Characterizing microglia EVs by means of Western blot analysis and other techniques revealed these EVs to be rich in TGF-β1. The latter turned out to be a key compound for the therapeutic potential of microglia EVs, affecting the Smad2/3 pathway in both ECs and neurons. EV infusion in stroke mice confirmed the aforementioned in vitro results, demonstrating an activation of the TGF-β/Smad2/3 signaling pathway within the ischemic brain. Furthermore, enriched TGF-β1 in EVs secreted from OGD-preconditioned microglia stimulated M2 polarization of residing microglia within the ischemic cerebral environment, which may contribute to a regulation of an early inflammatory response in postischemic hemispheres. These observations are not only interesting from the mechanistic point of view but have an immediate therapeutic implication as well, since stroke mice treated with such EVs displayed a better functional recovery in the behavioral test analyses. Hence, the present findings suggest a new way of action of EVs derived from OGD-preconditioned microglia by regulating the TGF-β/Smad2/3 pathway in order to promote tissue regeneration and neurological recovery in stroke mice.
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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.