{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T16:22:29Z","timestamp":1777998149863,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T00:00:00Z","timestamp":1744329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Advancing Translational Sciences (NCATS)","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}]},{"name":"the Waters Foundation","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}]},{"name":"the University of Georgia Wilson Pharmacy Foundation","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}]},{"name":"Charlie Norwood VA Medical Center","award":["UL1TR002378"],"award-info":[{"award-number":["UL1TR002378"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The role of claudin-17 (Cldn17), a tight-junction protein, in vascular permeability remains unclear. We investigated the impact of Cldn17 suppression on vascular permeability. The Miles assay demonstrated significantly increased vascular permeability in the lungs and skin of Cldn17\u2212\/\u2212 mice, as evidenced by elevated Evan\u2019s blue dye extravasation. The Matrigel plug assay demonstrated increased hemoglobin extravasation. Histopathological analysis revealed alveolar flooding, inflammatory cell infiltration, and lung injury in Cldn17\u2212\/\u2212 lungs. Wet\/dry lung weight ratios indicated pulmonary edema, supporting the role of Cldn17 in pulmonary fluid balance, which was exacerbated with lipopolysaccharide administration. Ribosomal nucleic acid sequencing identified distinct transcriptional changes, with the principal component analysis showing clear clustering. Differential gene expression analysis highlighted significant alterations in inflammatory and metabolic pathways. Gene ontology and pathway enrichment analyses revealed the upregulation of immune-related processes, including leukocyte adhesion, interferon\u2013gamma response, and neutrophil degranulation, alongside metabolic dysregulation affecting lipid transport and cytoskeletal organization. Reactome pathway analysis implicated Cldn17 in antigen presentation, interleukin-17 signaling, and inflammatory responses. These findings establish Cldn17 as a critical regulator of vascular permeability and immune homeostasis. Its deficiency drives vascular leakage, exacerbates lung injury, and alters immune signaling pathways, underscoring its potential as a therapeutic target for inflammatory lung diseases.<\/jats:p>","DOI":"10.3390\/ijms26083612","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T06:45:31Z","timestamp":1744353931000},"page":"3612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Claudin-17 Deficiency Drives Vascular Permeability and Inflammation Causing Lung Injury"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2129-1228","authenticated-orcid":false,"given":"Mir S.","family":"Adil","sequence":"first","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Varun","family":"Parvathagiri","sequence":"additional","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulaziz H.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daulat","family":"Khulood","sequence":"additional","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8842-622X","authenticated-orcid":false,"given":"S. Priya","family":"Narayanan","sequence":"additional","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3017-0230","authenticated-orcid":false,"given":"Payaningal R.","family":"Somanath","sequence":"additional","affiliation":[{"name":"Program in Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA 30912, USA"},{"name":"Research Division, Charlie Norwood VA Medical Center, Augusta, GA 30912, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1146\/annurev-pathol-012615-044506","article-title":"Disorders of Vascular Permeability","volume":"11","year":"2016","journal-title":"Annu. 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