ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
AKAP12 regulates human blood-retinal barrier formation by downregulation of hypoxia-inducible factor-1alpha.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 97 citations in OpenAlex.
- Advances in Modeling the Inner Blood-Retinal Barrier: From Static Tissue Cell Cultures to Microphysiological Systems.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Review
- Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood-brain barrier integrity.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Role of A-Kinase Anchoring Protein 12 in the Central Nervous System.Journal of clinical neurology (Seoul, Korea) · 2023Review
- Review
- The supplementation of a high dose of fish oil during pregnancy and lactation led to an elevation in Mfsd2a expression without any changes in docosahexaenoic acid levels in the retina of healthy 2-month-old mouse offspring.Frontiers in nutrition · 2023Article
- Mechanisms of macular edema.Frontiers in medicine · 2023Review
- An Altered Neurovascular System in Aging-Related Eye Diseases.International journal of molecular sciences · 2022Review
- Pan-cancer analysis of the prognosis and immunological role of AKAP12: A potential biomarker for resistance to anti-VEGF inhibitors.Frontiers in genetics · 2022Article
- Wnt Signaling in Inner Blood-Retinal Barrier Maintenance.International journal of molecular sciences · 2021Review
- Role of ginseng in the neurovascular unit of neuroinflammatory diseases focused on the blood-brain barrier.Journal of ginseng research · 2021Article
- Hypoxia Pathway Proteins and Their Impact on the Blood Vasculature.International journal of molecular sciences · 2021Review
- Roles of A-kinase Anchor Protein 12 in Astrocyte and Oligodendrocyte Precursor Cell in Postnatal Corpus Callosum.Stem cell reviews and reports · 2021Article
- Review
- Regulation of Endothelial and Vascular Functions by Carbon MonoxideFrontiers in cardiovascular medicine · 2021Review
- AKAP12 Supports Blood-Brain Barrier Integrity against Ischemic Stroke.International journal of molecular sciences · 2020Article
- Regulation of blood-retinal barrier cell-junctions in diabetic retinopathy.Pharmacological research · 2020Review
- AKAP12 Signaling Complex: Impacts of Compartmentalizing cAMP-Dependent Signaling Pathways in the Heart and Various Signaling Systems.Journal of the American Heart Association · 2020Review
- The Role of a Neurovascular Signaling Pathway Involving Hypoxia-Inducible Factor and Notch in the Function of the Central Nervous System.Biomolecules & therapeutics · 2020Review
- AKAP12 deficiency impairs VEGF-induced endothelial cell migration and sprouting.Acta physiologica (Oxford, England) · 2020Article
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Authors and funding
11 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many diseases of the eye such as retinoblastoma, diabetic retinopathy, and retinopathy of prematurity are associated with blood-retinal barrier (BRB) dysfunction. Identifying the factors that contribute to BRB formation during human eye development and maintenance could provide insights into such diseases. Here we show that A-kinase anchor protein 12 (AKAP12) induces BRB formation by increasing angiopoietin-1 and decreasing vascular endothelial growth factor (VEGF) levels in astrocytes. We reveal that AKAP12 downregulates the level of hypoxia-inducible factor-1alpha (HIF-1alpha) protein by enhancing the interaction of HIF-1alpha with pVHL (von Hippel-Lindau tumor suppressor protein) and PHD2 (prolyl hydroxylase 2). Conditioned media from AKAP12-overexpressing astrocytes induced barriergenesis by upregulating the expression of tight junction proteins in human retina microvascular endothelial cells (HRMECs). Compared with the retina during BRB maturation, AKAP12 expression in retinoblastoma patient tissue was markedly reduced whereas that of VEGF was increased. These findings suggest that AKAP12 may induce BRB formation through antiangiogenesis and barriergenesis in the developing human eye and that defects in this mechanism can lead to a loss of tight junction proteins and contribute to the development of retinal pathologies such as retinoblastoma.
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Registered trials
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