Pard3 promotes corneal epithelial stratification and homeostasis by regulating apical-basal polarity, cytoskeletal organization and tight junction-mediated barrier function
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
40188986
DOI
10.1016/j.jtos.2025.04.001
PII: S1542-0124(25)00054-0
Knihovny.cz E-zdroje
- Klíčová slova
- Apical-basal polarity, Barrier function, Corneal epithelium, Par3, Par6, Pard3, Stratification, Tight junction,
- MeSH
- adaptorové proteiny signální transdukční * MeSH
- cytoskelet * metabolismus MeSH
- homeostáza fyziologie MeSH
- mikroskopie elektronová rastrovací MeSH
- myši MeSH
- polarita buněk * fyziologie MeSH
- rohovkový epitel * metabolismus ultrastruktura MeSH
- těsný spoj * metabolismus fyziologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adaptorové proteiny signální transdukční * MeSH
PURPOSE: To document the expression of apical-basal polarity (ABP) determinants in the mouse corneal epithelium (CE) and elucidate the functions of Pard3 in establishment and maintenance of ABP, stratification, homeostasis, and barrier function in the CE. METHODS: Pard3Δ/ΔC mice (Pard3LoxP/LoxP; Aldh3A1-Cre/+) with cornea-specific Pard3 ablation were generated by breeding Aldh3A1-Cre/+ with Pard3LoxP/LoxP mice. The control (Aldh3A1-Cre/+ or Pard3LoxP/LoxP alone) and Pard3Δ/ΔC corneal histology, ocular surface properties, barrier function, and actin cytoskeleton were assessed by Haematoxylin and Eosin staining of paraformaldehyde-fixed, paraffin-embedded tissues, scanning electron microscopy, fluorescein staining, and phalloidin staining, respectively. The expression of specific markers of interest was evaluated by qRT-PCR, immunoblots and immunofluorescent staining. RESULTS: Dynamic changes were observed in the expression and localization of ABP determinants as the CE stratified and matured between post-natal day 5 (PN5) and PN52. Adult Pard3Δ/ΔC CE contained fewer cell layers with rounded basal cells, and loosely adherent superficial cells lacking microplicae. Adult Pard3Δ/ΔC CE also displayed impaired barrier function with decreased expression of tight junction, adherens junction, and desmosome components, disrupted actin cytoskeletal organization, increased proliferation, and upregulation of transcription factors that drive epithelial-mesenchymal transition (EMT). CONCLUSIONS: Disruption of ABP in Pard3Δ/ΔC CE, altered expression of cell junction complex components and disorganized actin cytoskeleton, increased cell proliferation, and upregulated EMT transcription factors suggest that the ABP-determinant Pard3 promotes CE features while suppressing mesenchymal cell fate. Collectively, these results elucidate that Pard3-mediated ABP is essential for CE stratification, homeostasis and barrier function.
Department of Molecular Biology Yokohama City University Yokohama Japan
Department of Ophthalmology University of South Florida Tampa FL USA
Institute of Molecular Genetics of the ASCR Prague Czech Republic
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