ArticleInvestigative ophthalmology & visual science2017
Spatiotemporally Controlled Ablation of Klf5 Results in Dysregulated Epithelial Homeostasis in Adult Mouse Corneas.
Article in Investigative ophthalmology & visual science, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 15 citations in OpenAlex.
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- PAX6 Deficiency Compromises the Ability of Limbal Epithelial Stem Cells to Properly Differentiate Into Mature Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2026Article
- IFITM1/OVOL1 Axis Is a Novel Regulator of the Expansion of the Limbal Epithelial Stem/Early Transient Amplifying Cell Population.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Activation of limbal epithelial proliferation is partly controlled by the ACE2-LCN2 pathway.iScience · 2024Article
- The single-cell transcriptomic atlas and RORA-mediated 3D epigenomic remodeling in driving corneal epithelial differentiation.Nature communications · 2024Article
- Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery.The ocular surface · 2023Review
- ETS1-HMGA2 Axis Promotes Human Limbal Epithelial Stem Cell Proliferation.Investigative ophthalmology & visual science · 2023Article
- Comprehensive 3D epigenomic maps define limbal stem/progenitor cell function and identity.Nature communications · 2022Article
- The Lacritin-Syndecan-1-Heparanase Axis in Dry Eye Disease.Advances in experimental medicine and biology · 2020Review
- Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration.The ocular surface · 2020Review
- Influence of Vitamin D on Corneal Epithelial Cell Desmosomes and Hemidesmosomes.Investigative ophthalmology & visual science · 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
- Corneal epithelial development and homeostasis.Differentiation; research in biological diversityReview
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Authors and funding
5 authors at 1 institution in 1 country.
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Abstract
Purpose: Corneal epithelial (CE) homeostasis requires coordination between proliferation and differentiation. Here we examine the role of cell proliferation regulator Krüppel-like factor 5 (Klf5) in adult mouse CE homeostasis. Methods: Klf5 was ablated in a spatiotemporally restricted manner by inducing Cre expression in 8-week-old ternary transgenic Klf5LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre (Klf5Δ/ΔCE) mouse CE by administering doxycycline via chow. Normal chow-fed ternary transgenic siblings served as controls. The control and Klf5Δ/ΔCE corneal (1) histology, (2) cell proliferation, and (3) Klf5-target gene expression were examined using (1) periodic acid Schiff reagent-stained sections, (2) Ki67 expression, and (3) quantitative PCR and immunostaining, respectively. The effect of KLF4, KLF5, and OCT1 on gastrokine-1 (GKN1) promoter activity was determined by transient transfection in human skin keratinocyte NCTC-2544 cells. Results: Klf5 expression was decreased to 23% of the controls in Klf5Δ/ΔCE corneas, which displayed increased fluorescein uptake, downregulation of tight junction proteins Tjp1 and Gkn1, desmosomal Dsg1a, and basement membrane Lama3 and Lamb1, suggesting defective permeability barrier. In transient transfection assays, KLF5 and OCT1 synergistically stimulated GKN1 promoter activity. Klf5Δ/ΔCE CE displayed significantly fewer cell layers and Ki67+ proliferative cells coupled with significantly decreased cyclin-D1, and elevated phospho(Ser-10) p27/Kip1 expression. Expression of Krt12, E-cadherin, and β-catenin remained unaltered in Klf5Δ/ΔCE corneas. Conclusions: Klf5 contributes to adult mouse CE homeostasis by promoting (1) permeability barrier function through upregulation of Tjp1, Gkn1, Dsg1a, Lama3, and Lamb1, and (2) basal cell proliferation through upregulation of cyclin-D1 and suppression of phospho(Ser-10) p27/Kip1, without significantly affecting the expression of epithelial markers Krt12, E-cadherin, and β-catenin.
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