ArticleInternational journal of molecular sciences2020
α1AMP-Activated Protein Kinase Protects against Lipopolysaccharide-Induced Endothelial Barrier Disruption via Junctional Reinforcement and Activation of the p38 MAPK/HSP27 Pathway.
Article in International journal of molecular sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 14 citations in OpenAlex.
- Sustainable Grape Antioxidant Dietary Fiber Preserves Proximal Colonic Homeostasis via Hsp27 and AMPK Signaling.International journal of molecular sciences · 2025Article
- Amphiregulin orchestrates the paracrine immune-suppressive function of amniotic-derived cells through its interplay with COX-2/PGEiScience · 2024Article
- Vascular leak in sepsis: physiological basis and potential therapeutic advances.Critical care (London, England) · 2024Review
- Impact of Non-Invasive Physical Plasma on Heat Shock Protein Functionality in Eukaryotic Cells.Biomedicines · 2023Article
- Metformin Preserves VE-Cadherin in Choroid Plexus and Attenuates Hydrocephalus via VEGF/VEGFR2/p-Src in an Intraventricular Hemorrhage Rat Model.International journal of molecular sciences · 2022Article
- Protection by metformin against severe Covid-19: An in-depth mechanistic analysis.Diabetes & metabolism · 2022Review
- Connexin and Pannexin Large-Pore Channels in Microcirculation and Neurovascular Coupling Function.International journal of molecular sciences · 2022Review
- Canagliflozin protects against sepsis capillary leak syndrome by activating endothelial α1AMPK.Scientific reports · 2021Article
- Atypical p38 Signaling, Activation, and Implications for Disease.International journal of molecular sciences · 2021Review
- AMP-activated protein kinase is a key regulator of acute neurovascular permeability.Journal of cell science · 2021Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Vascular hyperpermeability is a determinant factor in the pathophysiology of sepsis. While, AMP-activated protein kinase (AMPK) is known to play a role in maintaining endothelial barrier function in this condition. Therefore, we investigated the underlying molecular mechanisms of this protective effect. α1AMPK expression and/or activity was modulated in human dermal microvascular endothelial cells using either α1AMPK-targeting small interfering RNA or the direct pharmacological AMPK activator 991, prior to lipopolysaccharide (LPS) treatment. Western blotting was used to analyze the expression and/or phosphorylation of proteins that compose cellular junctions (zonula occludens-1 (ZO-1), vascular endothelial cadherin (VE-Cad), connexin 43 (Cx43)) or that regulate actin cytoskeleton (p38 MAPK; heat shock protein 27 (HSP27)). Functional endothelial permeability was assessed by in vitro Transwell assays, and quantification of cellular junctions in the plasma membrane was assessed by immunofluorescence. Actin cytoskeleton remodeling was evaluated through actin fluorescent staining. We consequently demonstrate that α1AMPK deficiency is associated with reduced expression of CX43, ZO-1, and VE-Cad, and that the drastic loss of CX43 is likely responsible for the subsequent decreased expression and localization of ZO-1 and VE-Cad in the plasma membrane. Moreover, α1AMPK activation by 991 protects against LPS-induced endothelial barrier disruption by reinforcing cortical actin cytoskeleton. This is due to a mechanism that involves the phosphorylation of p38 MAPK and HSP27, which is nonetheless independent of the small GTPase Rac1. This results in a drastic decrease of LPS-induced hyperpermeability. We conclude that α1AMPK activators that are suitable for clinical use may provide a specific therapeutic intervention that limits sepsis-induced vascular leakage.
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Registered trials
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