{"doi":"10.1002/jcp.24274","title":"src family kinases regulate renal epithelial paracellular permeability barrier through an occludin‐independent mechanism","abstract":"<jats:title>Abstract</jats:title><jats:p>Paracellular permeability is mediated by the epithelial cell tight junction. Studies in intestinal and other epithelia have suggested that the activity of src family kinases (SFKs) increases epithelial paracellular permeability through its action on the tight junction protein, occludin, but the involvement of SFKs and occludin in regulation of renal epithelial paracellular permeability is unclear. In this study, the role of SFKs in regulation of renal epithelial paracellular permeability and the involvement of occludin protein in this regulatory event was examined in two renal epithelial cell lines, LLC‐PK<jats:sub>1</jats:sub> (proximal tubule‐like) and MDCK (distal tubule‐like). The effect of broad spectrum SFK inhibitors on paracellular permeability of calcein and fluorescein‐dextran3000 were examined. SFK inhibitor treatment increased paracellular movement of both compounds in both renal epithelial cell lines. The SFK inhibitor effect was concentration‐dependent and, at low concentrations, was not associated with cell damage/death. Response to SFK inhibitors was acquired progressively after cell populations attained confluence suggesting maturation of the regulatory mechanism. Increased paracellular permeability was not associated with dramatic changes in total cell content of occludin protein, its partitioning between detergent‐soluble and ‐insoluble fractions, or its subcellular localization. Further, the SFK‐induced increase in paracellular permeability was unaffected by either occludin protein overexpression or occludin protein knockdown. These results demonstrate that SFK activity decreases paracellular permeability of renal epithelial cells, as opposed to its effect in intestinal epithelial cells, and that this regulation is not mediated by occludin protein. J. Cell. Physiol. 228: 1210–1220, 2013. © 2012 Wiley Periodicals, Inc.</jats:p>","journal":"Journal of Cellular Physiology","year":2013,"id":43579,"datarank":0.8921007797429592,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.4585450160585345,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.4585450160585345,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":10,"citers_with_citation_signal":7,"citers_with_endowment":7,"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":206766,"name":"Shuchie Jaggi","orcid":null,"position":1,"is_corresponding":false},{"id":206767,"name":"Josephine Axis","orcid":null,"position":2,"is_corresponding":false},{"id":206768,"name":"Kurt Amsler","orcid":null,"position":3,"is_corresponding":false},{"id":206765,"name":"Devin Caswell","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23129414","pmcid":null,"openalex_id":"https://openalex.org/W2048730687","authors":[],"funders":[],"total_grants":0,"fwci":0.8026,"citation_percentile":0.76308339,"influential_citations":0,"citation_trend":[{"year":2013,"count":1},{"year":2014,"count":1},{"year":2015,"count":2},{"year":2018,"count":3},{"year":2019,"count":1},{"year":2020,"count":3},{"year":2021,"count":2},{"year":2022,"count":2},{"year":2024,"count":2}],"oa_status":"closed","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fjcp.24274","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/jcp.24274","host_type":"publisher"},{"url":"https://doi.org/10.1002/jcp.24274","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23129414","host_type":"repository"}],"fields_of_study":["Barrier Structure and Function Studies","Drug Transport and Resistance Mechanisms","Epigenetics and DNA Methylation","Medicine","Biology","Actins","Animals","Dextrans","Dogs","Dose-Response Relationship, Drug","Epithelial Cells","Fluoresceins","Kidney Tubules","LLC-PK1 Cells","Madin Darby Canine Kidney Cells","Occludin","Permeability","Protein Kinase Inhibitors","Protein Transport","Swine","Tight Junctions","Time Factors","Transfection","Zonula Occludens-1 Protein","Zonula Occludens-2 Protein","src-Family Kinases"],"mesh_terms":["Actins","Animals","Dextrans","Dogs","Dose-Response Relationship, Drug","Epithelial Cells","Fluoresceins","Kidney Tubules","Permeability","Swine","Time Factors","Transfection","LLC-PK1 Cells","src-Family Kinases","Tight Junctions","Protein Transport","Protein Kinase Inhibitors","Madin Darby Canine Kidney Cells","Occludin","Zonula Occludens-1 Protein","Zonula Occludens-2 Protein"],"keywords":["Occludin","Paracellular transport","Tight junction","Cell biology","Claudin","Cell junction","Biology","Chemistry","Proto-oncogene tyrosine-protein kinase Src","Signal transduction","Permeability (electromagnetism)","Cell","Biochemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-06-15T01:05:59.975864Z","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":[]}