ArticleMediators of inflammation2017
AM966, an Antagonist of Lysophosphatidic Acid Receptor 1, Increases Lung Microvascular Endothelial Permeability through Activation of Rho Signaling Pathway and Phosphorylation of VE-Cadherin.
Article in Mediators of inflammation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 24 citations in OpenAlex.
- Possible Involvement of Lysophospholipids in Severe Asthma as Novel Lipid Mediators.Biomolecules · 2025Review
- Lysophosphatidic acid 2 alleviates deep vein thrombosis via protective endothelial barrier function.Open medicine (Warsaw, Poland) · 2025Article
- Inhibition of RhoA Prevents Cryptococcus neoformans Capsule Glucuronoxylomannan-Stimulated Brain Endothelial Barrier Disruption.The Journal of infectious diseases · 2024Article
- Article
- LPAJournal of inflammation research · 2023Article
- The ATX-LPA Axis Regulates Vascular Permeability during Cerebral Ischemic-Reperfusion.International journal of molecular sciences · 2022Article
- Lysophospholipids in Lung Inflammatory Diseases.Advances in experimental medicine and biology · 2021Article
- Anfibatide Preserves Blood-Brain Barrier Integrity by Inhibiting TLR4/RhoA/ROCK Pathway After Cerebral Ischemia/Reperfusion Injury in Rat.Journal of molecular neuroscience : MN · 2020Article
- Autophagy, Unfolded Protein Response and Lung Disease.Current research in cell biology · 2020Article
- Article
- Targeting Lysophosphatidic Acid in Cancer: The Issues in Moving from Bench to Bedside.Cancers · 2019Review
- The roles of nuclear focal adhesion kinase (FAK) on Cancer: a focused review.Journal of experimental & clinical cancer research : CR · 2019Review
- Novel mechanisms regulating endothelial barrier function in the pulmonary microcirculation.The Journal of physiology · 2019Review
- RAB26-dependent autophagy protects adherens junctional integrity in acute lung injury.Autophagy · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Maintenance of pulmonary endothelial barrier integrity is important for reducing severity of lung injury. Lysophosphatidic acid (LPA) regulates cell motility, cytoskeletal rearrangement, and cell growth. Knockdown of LPA receptor 1 (LPA1) has been shown to mitigate lung injury and pulmonary fibrosis. AM966, an LPA1 antagonist exhibiting an antifibrotic property, has been considered to be a future antifibrotic medicine. Here, we report an unexpected effect of AM966, which increases lung endothelial barrier permeability. An electric cell-substrate sensing (ECIS) system was used to measure permeability in human lung microvascular endothelial cells (HLMVECs). AM966 decreased the transendothelial electrical resistance (TEER) value immediately in a dose-dependent manner. VE-cadherin and f-actin double immunostaining reveals that AM966 increases stress fibers and gap formation between endothelial cells. AM966 induced phosphorylation of myosin light chain (MLC) through activation of RhoA/Rho kinase pathway. Unlike LPA treatment, AM966 had no effect on phosphorylation of extracellular signal-regulated kinases (Erk). Further, in LPA1 silencing cells, we observed that AM966-increased lung endothelial permeability as well as phosphorylation of VE-cadherin and focal adhesion kinase (FAK) were attenuated. This study reveals that AM966 induces lung endothelial barrier dysfunction, which is regulated by LPA1-mediated activation of RhoA/MLC and phosphorylation of VE-cadherin.
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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.