ArticleInvestigative ophthalmology & visual science2020
KLF4 Coordinates Corneal Epithelial Apical-Basal Polarity and Plane of Cell Division and Is Downregulated in Ocular Surface Squamous Neoplasia.
Article in Investigative ophthalmology & visual science, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 16 citations in OpenAlex.
- Apicobasal Polarity Protein PARD3 Plays an Essential Role in Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2026Article
- Identification of dysregulated gene clusters and pathways driving ocular surface squamous neoplasia progression.Scientific reports · 2025Article
- Pard3 promotes corneal epithelial stratification and homeostasis by regulating apical-basal polarity, cytoskeletal organization and tight junction-mediated barrier function.The ocular surface · 2025Article
- Construction and validation of a nomogram model for predicting peritoneal metastasis in gastric cancer based on ferroptosis-relate genes and clinicopathological features.Journal of gastrointestinal oncology · 2025Article
- A dynamic co-expression approach reveals Gins2 as a potential upstream modulator of HNSCC metastasis.Scientific reports · 2025Article
- The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3.International journal of molecular sciences · 2024Article
- Clinically correlated dose of the amniotic membrane extract is superior to its transplantation in corneal wound healing.Molecular vision · 2024Article
- Intercellular Communication in Airway Epithelial Cell Regeneration: Potential Roles of Connexins and Pannexins.International journal of molecular sciences · 2023Review
- Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery.The ocular surface · 2023Review
- KLF4 transcription factor in tumorigenesis.Cell death discovery · 2023Review
- Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED).Pathogens (Basel, Switzerland) · 2023Article
- Secreted Ly-6/uPAR-related protein-1 (SLURP1) is a pro-differentiation factor that stalls G1-S transition during corneal epithelial cell cycle progression.The ocular surface · 2022Article
- Cascade of Inflammatory, Fibrotic Processes, and Stress-Induced Senescence in Chronic GVHD-Related Dry Eye Disease.International journal of molecular sciences · 2021Review
- Transcriptomic and Immunohistochemical Analysis of Progressive Keratoconus Reveal Altered WNT10A in Epithelium and Bowman's Layer.Investigative ophthalmology & visual science · 2021Article
- Corneal epithelial development and homeostasis.Differentiation; research in biological diversityReview
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: Previously, we demonstrated that Krüppel-like factor 4 (KLF4) promotes corneal epithelial (CE) homeostasis by suppressing epithelial-mesenchymal transition (EMT) and TGF-β signaling. As TGF-β affects epithelial apicobasal polarity (ABP) and plane of division, we investigated the role of KLF4 in these processes. Methods: Klf4 was ablated in adult ternary transgenic Klf4Δ/ΔCE (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mouse CE using doxycycline chow. ABP and plane of division markers' expression in Klf4Δ/ΔCE and human ocular surface squamous neoplasia (OSSN) tissues relative to controls was evaluated by quantitative PCR, immunoblots, and/or immunofluorescent staining. Results: Klf4Δ/ΔCE CE cells displayed downregulation of apical Pals1 and Crumbs1, apicolateral Par3, and basolateral Scribble, as well as upregulation of Rho family GTPase Cdc42, suggesting disruption of ABP. Phalloidin staining revealed that the Klf4Δ/ΔCE CE actin cytoskeleton is disrupted. Klf4Δ/ΔCE cells favored vertical plane of division within 67.5° to 90° of the CE basement membrane (39% and 47% of the dividing cells relative to 23% and 26% in the control based on phospho-histone-H3 and survivin, respectively), resulting in more dividing cells within the Klf4Δ/ΔCE CE as reported previously. KLF4 was downregulated in human OSSN tissues that displayed EMT and downregulation of PAR3, PALS1, and SCRIB, consistent with a protective role for KLF4. Conclusions: By demonstrating that Klf4 ablation affects CE expression of ABP markers and Cdc42, cytoskeletal actin organization, and the plane of cell division and that KLF4 is downregulated in OSSN tissues that display EMT and lack ABP, these results elucidate the key integrative role of KLF4 in coordinating CE cell polarity and plane of division, loss of which results in OSSN.
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