ArticleNature medicine2013
Endothelial TWIK-related potassium channel-1 (TREK1) regulates immune-cell trafficking into the CNS.
Article in Nature medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 160 citations in OpenAlex.
- The omega-3 and Nano-curcumin effects on vascular cell adhesion molecule (VCAM) in episodic migraine patients: a randomized clinical trial.BMC research notes · 2021Trial
- Role for TREK-1 as a polymodal sensor and regulator of cell activity.Channels (Austin, Tex.) · 2026Review
- Recent advances in self-assembled nanoplatforms for central nervous system disorders therapy: Design principles, multifunctional strategies, and therapeutic applications.Materials today. Bio · 2026Review
- Channel Dysfunction as the Basis for Comorbidities in Multiple Sclerosis and Depression.Archiv der Pharmazie · 2026Review
- Structure-Function Relationships of KAdvances in experimental medicine and biology · 2026Review
- Modulating glutamate neurotransmission inFrontiers in immunology · 2026Review
- Shared Disease Mechanisms in Neurodevelopmental Disorders: A Cellular and Molecular Biology Perspective.Brain sciences · 2025Review
- Pathways, Mechanisms, and Therapeutic Strategies of Neurotoxicity Induced by Micro- and Nanoplastics.Brain sciences · 2025Review
- TREK- 1 Ameliorates Secondary Brain Injury by Regulating Inflammatory Microenvironment via CX3 CL1-CX3 CR1 Pathway After Intracerebral Hemorrhage.Molecular neurobiology · 2025Article
- The potassium channel KNature communications · 2025Article
- Article
- Oligodendrocyte and Myelin Pathophysiology in Multiple Sclerosis.Advances in neurobiology · 2025Review
- KPflugers Archiv : European journal of physiology · 2025Article
- Long-Term Follow-Up before and during Riluzole Treatment in Six Patients from Two Families with Spinocerebellar Ataxia Type 7.Cerebellum (London, England) · 2024Article
- Endothelial EGLN3-PKM2 signaling induces the formation of acute astrocytic barrier to alleviate immune cell infiltration after subarachnoid hemorrhage.Fluids and barriers of the CNS · 2024Article
- Teriflunomide Promotes Blood-Brain Barrier Integrity by Upregulating Claudin-1 via the Wnt/β-catenin Signaling Pathway in Multiple Sclerosis.Molecular neurobiology · 2024Article
- Inflammation-induced TRPV4 channels exacerbate blood-brain barrier dysfunction in multiple sclerosis.Journal of neuroinflammation · 2024Article
- Ion Channel Dysregulation Following Intracerebral Hemorrhage.Neuroscience bulletin · 2024Review
- Kv7 channel activation reduces brain endothelial cell permeability and prevents kainic acid-induced blood-brain barrier damage.American journal of physiology. Cell physiology · 2024Article
- The neurovasculature as a target in temporal lobe epilepsy.Brain pathology (Zurich, Switzerland) · 2023Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The blood-brain barrier (BBB) is an integral part of the neurovascular unit (NVU). The NVU is comprised of endothelial cells that are interconnected by tight junctions resting on a parenchymal basement membrane ensheathed by pericytes, smooth muscle cells and a layer of astrocyte end feet. Circulating blood cells, such as leukocytes, complete the NVU. BBB disruption is common in several neurological diseases, but the molecular mechanisms involved remain largely unknown. We analyzed the role of TWIK-related potassium channel-1 (TREK1, encoded by KCNK2) in human and mouse endothelial cells and the BBB. TREK1 was downregulated in endothelial cells by treatment with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Blocking TREK1 increased leukocyte transmigration, whereas TREK1 activation had the opposite effect. We identified altered mitogen-activated protein (MAP) kinase signaling, actin remodeling and upregulation of cellular adhesion molecules as potential mechanisms of increased migration in TREK1-deficient (Kcnk2(-/-)) cells. In Kcnk2(-/-) mice, brain endothelial cells showed an upregulation of the cellular adhesion molecules ICAM1, VCAM1 and PECAM1 and facilitated leukocyte trafficking into the CNS. Following the induction of experimental autoimmune encephalomyelitis (EAE) by immunization with a myelin oligodendrocyte protein (MOG)35-55 peptide, Kcnk2(-/-) mice showed higher EAE severity scores that were accompanied by increased cellular infiltrates in the central nervous system (CNS). The severity of EAE was attenuated in mice given the amyotrophic lateral sclerosis drug riluzole or fed a diet enriched with linseed oil (which contains the TREK-1 activating omega-3 fatty acid α-linolenic acid). These beneficial effects were reduced in Kcnk2(-/-) mice, suggesting TREK-1 activating compounds may be used therapeutically to treat diseases related to BBB dysfunction.
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