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Claudin-17 Deficiency Drives Vascular Permeability and Inflammation Causing Lung Injury.
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- Additional Information
- Source:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
- Publication Information:
Original Publication: Basel, Switzerland : MDPI, [2000-
- Subject Terms:
- Abstract:
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 -/- mice, as evidenced by elevated Evan's blue dye extravasation. The Matrigel plug assay demonstrated increased hemoglobin extravasation. Histopathological analysis revealed alveolar flooding, inflammatory cell infiltration, and lung injury in Cldn17 -/- 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-gamma 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.
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- Grant Information:
1UL1TR002378-22A1 United States NH NIH HHS
- Contributed Indexing:
Keywords: Cldn17; inflammation; lung injury; pulmonary edema; vascular permeability
- Accession Number:
0 (Claudins)
0 (Lipopolysaccharides)
- Publication Date:
Date Created: 20250507 Date Completed: 20250507 Latest Revision: 20250509
- Publication Date:
20250509
- Accession Number:
PMC12027279
- Accession Number:
10.3390/ijms26083612
- Accession Number:
40332125
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