ArticlePloS one2012
Perlecan Domain V induces VEGf secretion in brain endothelial cells through integrin α5β1 and ERK-dependent signaling pathways.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Diverse and multifunctional roles for perlecan (JOR spine · 2024Review
- Molecular interactions between perlecan LG3 and the SARS-CoV-2 spike protein receptor binding domain.Protein science : a publication of the Protein Society · 2024Article
- Biomimetic strategies for the deputization of proteoglycan functions.Frontiers in cell and developmental biology · 2024Review
- Recombinant Human Perlecan DV and Its LG3 Subdomain Are Neuroprotective and Acutely Functionally Restorative in Severe Experimental Ischemic Stroke.Translational stroke research · 2023Article
- VEGFA Isoforms as Pro-Angiogenic Therapeutics for Cerebrovascular Diseases.Biomolecules · 2023Review
- The Potential Role of Integrin Signaling in Memory and Cognitive Impairment.Biomolecules · 2023Review
- Perlecan, A Multi-Functional, Cell-Instructive, Matrix-Stabilizing Proteoglycan With Roles in Tissue Development Has Relevance to Connective Tissue Repair and Regeneration.Frontiers in cell and developmental biology · 2022Review
- Extracellular Environment-Controlled Angiogenesis, and Potential Application for Peripheral Nerve Regeneration.International journal of molecular sciences · 2021Review
- Perlecan Domain-V Enhances Neurogenic Brain Repair After Stroke in Mice.Translational stroke research · 2021Article
- Review of Alterations in Perlecan-Associated Vascular Risk Factors in Dementia.International journal of molecular sciences · 2020Review
- The Stroke-Induced Blood-Brain Barrier Disruption: Current Progress of Inspection Technique, Mechanism, and Therapeutic Target.Current neuropharmacology · 2020Review
- Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke.Journal of neuroinflammation · 2019Article
- Perlecan regulates pericyte dynamics in the maintenance and repair of the blood-brain barrier.The Journal of cell biology · 2019Article
- Roles of blood-brain barrier integrins and extracellular matrix in stroke.American journal of physiology. Cell physiology · 2019Review
- Proteoglycans in Biomedicine: Resurgence of an Underexploited Class of ECM Molecules.Frontiers in pharmacology · 2019Review
- Article
- Effect of Intranasally Delivered rh-VEGF165 on Angiogenesis Following Cerebral Hypoxia-Ischemia in the Cerebral Cortex of Newborn Piglets.International journal of molecular sciences · 2017Article
- Mice deficient in endothelial α5 integrin are profoundly resistant to experimental ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- IL-1alpha induces angiogenesis in brain endothelial cells in vitro: implications for brain angiogenesis after acute injury.Journal of neurochemistry · 2016Article
- Proteoglycans: Potential Agents in Mammographic Density and the Associated Breast Cancer Risk.Journal of mammary gland biology and neoplasia · 2015Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction of DV with α(5)β(1). Furthermore, we investigated the importance of AKT and ERK signaling in DV-induced VEGF expression and secretion. We show that DV increases the phosphorylation of ERK, which leads to subsequent activation and stabilization of eIF4E and HIF-1α. Inhibition of ERK activity by U0126 suppressed DV-induced expression and secretion of VEGR in BECs. While DV was capable of phosphorylating AKT we show that AKT phosphorylation does not play a role in DV's induction of VEGF expression or secretion using two separate inhibitors, LY294002 and Akt IV. Lastly, we demonstrate that VEGF activity is critical for DV increases in BEC proliferation, as well as angiogenesis in a BEC-neuronal co-culture system. Collectively, our findings expand our understanding of DV's mechanism of action on BECs, and further support its potential as a novel stroke therapy.
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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.