ArticleInvestigative ophthalmology & visual science2015
Spatiotemporally Regulated Ablation of Klf4 in Adult Mouse Corneal Epithelial Cells Results in Altered Epithelial Cell Identity and Disrupted Homeostasis.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- The CXXC1-IGFBP6 Axis Maintains Corneal Epithelial Differentiation via H3K4me3-Dependent Transcriptional Activation.Investigative ophthalmology & visual science · 2026Article
- Analyzing cell-type-specific isoform expression using IsoDiffR and long-read single-cell RNA sequencing.Bioinformatics (Oxford, England) · 2026Article
- Pard3 promotes corneal epithelial stratification and homeostasis by regulating apical-basal polarity, cytoskeletal organization and tight junction-mediated barrier function.The ocular surface · 2025Article
- Krüppel-like factor 4 transcription factor in blood-brain barrier endothelial cells: A potential role in Alzheimer's disease.Animal models and experimental medicine · 2025Review
- Review
- Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery.The ocular surface · 2023Review
- Alterations in corneal biomechanics underlie early stages of autoimmune-mediated dry eye disease.Journal of autoimmunity · 2020Article
- BMP6 Regulates Corneal Epithelial Cell Stratification by Coordinating Their Proliferation and Differentiation and Is Upregulated in Pterygium.Investigative ophthalmology & visual science · 2020Article
- KLF4 Coordinates Corneal Epithelial Apical-Basal Polarity and Plane of Cell Division and Is Downregulated in Ocular Surface Squamous Neoplasia.Investigative ophthalmology & visual science · 2020Article
- Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration.The ocular surface · 2020Review
- KLF4 prevents epithelial to mesenchymal transition in human corneal epithelial cellsRegenerative therapy · 2019Article
- Molecular markers for corneal epithelial cells in larval vs. adult Xenopus frogs.Experimental eye research · 2019Article
- KLF4 Regulates Corneal Epithelial Cell Cycle Progression by Suppressing Canonical TGF-β Signaling and Upregulating CDK Inhibitors P16 and P27.Investigative ophthalmology & visual science · 2019Article
- Loss of the Krüppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer.Journal of cancer metastasis and treatment · 2019Article
- Spatiotemporally Controlled Ablation of Klf5 Results in Dysregulated Epithelial Homeostasis in Adult Mouse Corneas.Investigative ophthalmology & visual science · 2017Article
- KLF4 Plays an Essential Role in Corneal Epithelial Homeostasis by Promoting Epithelial Cell Fate and Suppressing Epithelial-Mesenchymal Transition.Investigative ophthalmology & visual science · 2017Article
- Corneal Expression of SLURP-1 by Age, Sex, Genetic Strain, and Ocular Surface Health.Investigative ophthalmology & visual science · 2015Article
- Corneal epithelial development and homeostasis.Differentiation; research in biological diversityReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeIn previous studies, conditional disruption of Klf4 in the developing mouse ocular surface from embryonic day 10 resulted in corneal epithelial fragility, stromal edema, and loss of conjunctival goblet cells, revealing the importance of Klf4 in ocular surface maturation. Here, we use spatiotemporally regulated ablation of Klf4 to investigate its functions in maintenance of adult corneal epithelial homeostasis.
methodsExpression of Cre was induced in ternary transgenic (Klf4(LoxP/LoxP)/Krt12(rtTA/rtTA)/Tet-O-Cre) mouse corneal epithelium by doxycycline administered through intraperitoneal injections and drinking water, to generate corneal epithelium-specific deletion of Klf4 (Klf4(Δ/ΔCE)). Corneal epithelial barrier function was tested by fluorescein staining. Expression of selected Klf4-target genes was determined by quantitative PCR (QPCR), immunoblotting, and immunofluorescent staining.
resultsKlf4 was efficiently ablated within 5 days of doxycycline administration in adult Klf4(Δ/ΔCE) corneal epithelium. The Klf4(Δ/ΔCE) corneal epithelial barrier function was disrupted, and the basal cells were swollen and rounded after 15 days of doxycycline treatment. Increased numbers of cell layers and Ki67-positive proliferating cells suggested deregulated Klf4(Δ/ΔCE) corneal epithelial homeostasis. Expression of tight junction proteins ZO-1 and occludin, desmosomal Dsg and Dsp, basement membrane laminin-332, and corneal epithelial-specific keratin-12 was decreased, while that of matrix metalloproteinase Mmp9 and noncorneal keratin-17 increased, suggesting altered Klf4(Δ/ΔCE) corneal epithelial cell identity.
conclusionsAblation of Klf4 in the adult mouse corneas resulted in the absence of characteristic corneal epithelial cell differentiation, disrupted barrier function, and squamous metaplasia, revealing that Klf4 is essential for maintenance of the adult corneal epithelial cell identity and homeostasis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.