{
  "abstract": "Dry eye disease (DED) is characterized by tear hyperosmolality and ocular surface injury, but the contribution of focal adhesion kinase (FAK)-related signaling to tight junction (TJ) protein alterations remains unclear. We combined a scopolamine hydrobromide (SCOP)-induced desiccating stress mouse model with human corneal epithelial (HCE-T) cells exposed to NaCl-induced hyperosmolarity, together with transcriptomics, immunofluorescence, immunoblotting, pharmacological inhibition, and siRNA-mediated FAK knockdown. RNA sequencing identified 823 significant large-effect differentially expressed genes; analysis of the 3741 FDR-corrected significant genes revealed significant enrichment of focal adhesion, extracellular matrix–receptor, cell adhesion, and tight junction pathways. In HCE-T cells, hyperosmotic stress increased FAK Tyr397 phosphorylation as early as 1 h without changing total FAK. At 24 h, p-FAK declined while total FAK protein levels remained stable, consistent with dephosphorylation at Tyr397; by 48 h, total FAK protein was lost, accompanied by cell injury. TJ protein abundance and junctional continuity decreased progressively with increasing osmolarity and exposure duration. PF-562271, a dual FAK/Pyk2 inhibitor, produced a concentration-dependent reduction in FAK Tyr397 phosphorylation and, at 2.5 μM, also reduced Pyk2 Tyr402 phosphorylation while partially preserving ZO-1, claudin-1, and occludin abundance. FAK knockdown independently attenuated TJ protein loss and partially preserved ZO-1 junctional continuity under 500 mOsm/L hyperosmotic stress. These findings support a time-dependent contribution of FAK-related signaling to hyperosmotic stress-induced TJ protein remodeling.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Ophthalmology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing 210022, China"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yumeng Zhou"
    },
    {
      "affs": [
        0
      ],
      "name": "Chuanxue Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying Gao"
    },
    {
      "affs": [
        0
      ],
      "name": "Yujun Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Zeyu Zhang"
    },
    {
      "affs": [
        0
      ],
      "name": "Mingjia Shi"
    },
    {
      "affs": [
        0
      ],
      "name": "Yi Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d9e0jm85k7tph.bib",
  "cited_by": 0,
  "doi": "10.3390/ijms27219716",
  "fulltext_url": null,
  "id": "d9e0jm85k7tph",
  "issns": [
    "1422-0067"
  ],
  "landing_url": "https://www.mdpi.com/1422-0067/27/21/9716",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": "MDPI AG",
  "ris": "https://research.draconitic.com/paper/d9e0jm85k7tph.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:58Z",
      "native_id": "10.3390/ijms27219716",
      "source": "crossref",
      "url": "https://www.mdpi.com/1422-0067/27/21/9716"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "issn:1422-0067",
      "subfield": "general"
    }
  ],
  "title": "Rapid FAK Phosphorylation and Progressive Tight-Junction Protein Alterations Under Hyperosmotic Stress in Corneal Epithelial Cells",
  "title_text": "Rapid FAK Phosphorylation and Progressive Tight-Junction Protein Alterations Under Hyperosmotic Stress in Corneal Epithelial Cells",
  "type": "peer-reviewed",
  "updated_at": "2026-10-31T00:20:54Z",
  "url": "https://research.draconitic.com/paper/d9e0jm85k7tph",
  "venue": "International Journal of Molecular Sciences",
  "versions": []
}