{"doi":"10.1007/s10456-009-9139-3","title":"Chloride intracellular channel 4 is involved in endothelial proliferation and morphogenesis in vitro","abstract":null,"journal":"Angiogenesis","year":2009,"id":618878,"datarank":0.6966586348712059,"base_score":4.6443908991413725,"endowment":4.6443908991413725,"self_citation_contribution":0.6966586348712059,"citation_network_contribution":0.0,"self_endowment_contribution":0.6966586348712059,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":103,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":188940,"name":"Oliver Hobert","orcid":null,"position":1,"is_corresponding":false},{"id":737852,"name":"Mark Berryman","orcid":null,"position":2,"is_corresponding":false},{"id":406909,"name":"Jan Kitajewski","orcid":"0000-0003-4660-593X","position":3,"is_corresponding":false},{"id":1596854,"name":"Jennifer J. Tung","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Chloride intracellular channel 4 is involved in endothelial proliferation and morphogenesis in vitro","abstract":"New capillaries are formed through angiogenesis and an integral step in this process is endothelial tubulogenesis. The molecular mechanisms driving tube formation during angiogenesis are not yet delineated. Recently, the chloride intracellular channel 4 (CLIC4)-orthologue EXC-4 was found to be necessary for proper development and maintenance of the Caenorhabditis elegans excretory canal, implicating CLIC4 as a regulator of tubulogenesis. Here, we studied the role of CLIC4 in angiogenesis and endothelial tubulogenesis. We report the effects of inhibiting or inducing CLIC4 expression on distinct aspects of endothelial cell behavior in vitro. Our experiments utilized RNA interference to establish cultured human endothelial cell lines with significant reduction of CLIC4 expression, and a CLIC4-expressing lentiviral plasmid was used to establish CLIC4 overexpression in endothelial cells. We observed no effect on cell migration and a modest effect on cell survival. Reduced CLIC4 expression decreased cell proliferation, capillary network formation, capillary-like sprouting, and lumen formation. This suggests that normal endogenous CLIC4 expression is required for angiogenesis and tubulogenesis. Accordingly, increased CLIC4 expression promoted proliferation, network formation, capillary-like sprouting, and lumen formation. We conclude that CLIC4 functions to promote endothelial cell proliferation and to regulate endothelial morphogenesis, and is thus involved in multiple steps of in vitro angiogenesis.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"19247789","pmcid":"PMC3893792","openalex_id":null,"authors":[],"funders":[{"funder_name":"NEI NIH HHS","grant_id":"T32 EY013933","title":null},{"funder_name":"NEI NIH HHS","grant_id":"T32 EY13933","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"R15 GM084414","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"T32 GM008224","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL062454","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL62454","title":null},{"funder_name":"National Institutes of Health","grant_id":"5T32EY013933-02","title":"Vision Sciences Training Grant"},{"funder_name":"Deutsche Forschungsgemeinschaft","grant_id":"24040814/EXC 4","title":"Nanosystems Initiative Munich (NIM)"},{"funder_name":"National Institutes of Health","grant_id":"2T32GM008224-16","title":"Training in Cellular, Molecular and Biophysical Studies"},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":10,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"Springer TDM","oa_locations":[{"url":"http://link.springer.com/content/pdf/10.1007/s10456-009-9139-3.pdf","host_type":"publisher"},{"url":"http://link.springer.com/article/10.1007/s10456-009-9139-3/fulltext.html","host_type":"publisher"},{"url":"http://link.springer.com/content/pdf/10.1007/s10456-009-9139-3","host_type":"publisher"},{"url":"https://doi.org/10.1007/s10456-009-9139-3","host_type":""},{"url":"https://europepmc.org/articles/pmc3893792?pdf=render","host_type":""},{"url":"https://pubmed.ncbi.nlm.nih.gov/19247789","host_type":""},{"url":"https://dx.doi.org/10.1007/s10456-009-9139-3","host_type":""}],"fields_of_study":["0301 basic medicine","0303 health sciences","03 medical and health sciences"],"mesh_terms":["Capillaries","Cells, Cultured","Endothelial Cells","Humans","Chloride Channels","RNA, Small Interfering","Cell Proliferation","Cell Movement","Morphogenesis","Neovascularization, Physiologic","Gene Knockdown Techniques"],"keywords":["Endothelial Cells","Neovascularization, Physiologic","Capillaries","Cell Movement","Chloride Channels","Gene Knockdown Techniques","Morphogenesis","Humans","RNA, Small Interfering","Cells, Cultured","Cell Proliferation"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-03T05:29:22.721377Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}