ArticleArteriosclerosis, thrombosis, and vascular biology2023
CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 20 citations in OpenAlex.
- High Glucose Alters Extracellular Vesicle Protein Composition and Promotes EV-Mediated Monocyte Adhesion to Endothelial Cells.International journal of molecular sciences · 2026Article
- Genetic determinants of insufficiency of the collateral circulation.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- A novel tRNA‑derived small RNA, 5'tiRNA‑Gln‑TTG‑001, aggravates cardiomyocyte inflammatory injury through upregulation of CLIC4.Molecular medicine reports · 2025Article
- Novel Function for Endothelial Protease-Activated Receptors in Modulating Insulin Receptor Activity With Implications for Diabetes.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- A multi-trait genome-wide association study of coronary artery disease and subclinical atherosclerosis traits.Research square · 2025Article
- The role of chloride intracellular channel 4 in tumors.Cancer cell international · 2025Review
- RGS2 is an innate immune checkpoint for suppressing Gαq-mediated IFNγ generation and lung injury.iScience · 2025Article
- Chloride intracellular channel (CLIC) protein function in S1P-induced Rac1 activation requires membrane localization of the C-terminus, but not thiol-transferase nor ion channel activities.Frontiers in cell and developmental biology · 2025Article
- Intracellular Chloride Channels: A Rising Target in Lung Disease Research.Journal of respiratory biology and translational medicine · 2025Article
- Acetaminophen Overdose Reveals PAR4 as a Low-Expressing but Potent Receptor on the Hepatic Endothelium in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Angiogenesis, a key point in the association of gut microbiota and its metabolites with disease.European journal of medical research · 2024Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEndothelial CLICs (chloride intracellular channel proteins) CLIC1 and CLIC4 are required for the GPCRs (G-protein-coupled receptors) S1PR1 (sphingosine-1-phosphate receptor 1) and S1PR3 to activate the small GTPases Rac1 (Ras-related C3 botulinum toxin substrate 1) and RhoA (Ras homolog family member A). To determine whether CLIC1 and CLIC4 function in additional endothelial GPCR pathways, we evaluated CLIC function in thrombin signaling via the thrombin-regulated PAR1 (protease-activated receptor 1) and downstream effector RhoA.
methodsWe assessed the ability of CLIC1 and CLIC4 to relocalize to cell membranes in response to thrombin in human umbilical vein endothelial cells (HUVEC). We examined CLIC1 and CLIC4 function in HUVEC by knocking down expression of each CLIC protein and compared thrombin-mediated RhoA or Rac1 activation, ERM (ezrin/radixin/moesin) phosphorylation, and endothelial barrier modulation in control and CLIC knockdown HUVEC. We generated a conditional murine allele of
resultsThrombin promoted relocalization of CLIC4, but not CLIC1, to HUVEC membranes. Knockdown of CLIC4 in HUVEC reduced thrombin-mediated RhoA activation, ERM phosphorylation, and endothelial barrier disruption. Knockdown of CLIC1 did not reduce thrombin-mediated RhoA activity but prolonged the RhoA and endothelial barrier response to thrombin. Endothelial-specific deletion of
conclusionsCLIC4 is a critical effector of endothelial PAR1 signaling and is required to regulate RhoA-mediated endothelial barrier disruption in cultured endothelial cells and murine lung endothelium. CLIC1 was not critical for thrombin-mediated barrier disruption but contributed to the barrier recovery phase after thrombin treatment.
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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 Socratic graph.