ArticleThe American journal of pathology2009
Chloride intracellular channel protein-4 functions in angiogenesis by supporting acidification of vacuoles along the intracellular tubulogenic pathway.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 118 citations in OpenAlex.
- A cryptic-site ligand stabilizes a non-canonical interface and blocks membrane insertion of the chloride intracellular channel CLIC1.The Journal of biological chemistry · 2026Article
- Genetic alterations in coronary cell lines exposed to sirolimus and paclitaxel.Archives of toxicology · 2025Article
- CLIC1 Supports Mechanisms Related to Platelet Activation and Thrombosis.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Article
- The role of chloride intracellular channel 4 in tumors.Cancer cell international · 2025Review
- Emerging Gene Therapy Based on Nanocarriers: A Promising Therapeutic Alternative for Cardiovascular Diseases and a Novel Strategy in Valvular Heart Disease.International journal of molecular sciences · 2025Review
- 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
- Chloride intracellular channel (CLIC) proteins function as fusogens.Nature communications · 2024Article
- CLIC4 Regulates Endothelial Barrier Control by Mediating PAR1 Signaling via RhoA.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Hungry for Chloride: Reprogramming Endothelial Cell Metabolism in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2023Article
- Intracellular Chloride Channels Regulate Endothelial Metabolic Reprogramming in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2023Article
- A metazoan-specific C-terminal motif in EXC-4 and Gα-Rho/Rac signaling regulate cell outgrowth during tubulogenesis in C. elegans.Development (Cambridge, England) · 2022Article
- Review
- Host CLIC4 expression in the tumor microenvironment is essential for breast cancer metastatic competence.PLoS genetics · 2022Article
- Ion channels as a therapeutic target for renal fibrosis.Frontiers in physiology · 2022Review
- Chloride intracellular channel 4 (CLIC4) expression profile in the mouse medial prefrontal cortex and its regulation by ethanol.Alcoholism, clinical and experimental research · 2022Article
- RNA-Seq analysis in giant pandas reveals the differential expression of multiple genes involved in cataract formation.BMC genomic data · 2021Article
- CLIC1 and CLIC4 mediate endothelial S1P receptor signaling to facilitate Rac1 and RhoA activity and function.Science signaling · 2021Article
- From Pinocytosis to Methuosis-Fluid Consumption as a Risk Factor for Cell Death.Frontiers in cell and developmental biology · 2021Review
- Article
- Census of halide-binding sites in protein structures.Bioinformatics (Oxford, England) · 2020Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Endothelial cells form capillary tubes through the process of intracellular tubulogenesis. Chloride intracellular channel (CLIC) family proteins have been previously implicated in intracellular tubulogenesis, but their specific role has not been defined. In this study, we show that disruption of the Clic4 gene in mice results in defective angiogenesis in vivo as reflected in a Matrigel plug angiogenesis assay. An angiogenesis defect is also apparent in the retina, both in the decreased spontaneous development of retinal vasculature of unstressed mice and in the dramatically decreased angiogenic response of retinal vessels to an oxygen toxicity challenge. We found that endothelial cells derived from Clic4(-/-) mice demonstrated impaired tubulogenesis in three-dimensional fibrin gels compared with cells derived from wild-type mice. Furthermore, we found that tubulogenesis of wild-type cells in culture was inhibited by both an inhibitor of CLICs and an inhibitor of the vacuolar proton ATPase. Finally, we showed that vacuoles along the endothelial tubulogenesis pathway are acidic in wild-type cells, and that vacuolar acidification is impaired in Clic4(-/-) cells while lysosomal acidification is intact. We conclude that CLIC4 plays a critical role in angiogenesis by supporting acidification of vacuoles along the cell-hollowing tubulogenic pathway.
Indexed as
Identifiers
What OpenQuestion holds
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.