ArticleInvestigative ophthalmology & visual science2019
KLF4 Regulates Corneal Epithelial Cell Cycle Progression by Suppressing Canonical TGF-β Signaling and Upregulating CDK Inhibitors P16 and P27.
Article in Investigative ophthalmology & visual science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- A multi-ethnic genome-wide association study implicates collagen matrix integrity and cell differentiation pathways in keratoconus.Communications biology · 2021Pooled it
- Key role of transcription factors network in proliferative vitreoretinal diseases development.Cell & bioscience · 2026Review
- Gastric neoplasm with foveolar-cell differentiation inHistology and histopathology · 2026Review
- Apicobasal Polarity Protein PARD3 Plays an Essential Role in Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2026Article
- Analyzing cell-type-specific isoform expression using IsoDiffR and long-read single-cell RNA sequencing.Bioinformatics (Oxford, England) · 2026Article
- Endocardial primary cilia and blood flow regulate EndoMT during endocardial cushion development.Nature cardiovascular research · 2025Article
- CDKN1A as a potential target for Eltrombopag treatment in ITP and its regulation of the communication between macrophages and transitional B cells in ITP.Annals of hematology · 2025Article
- Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery.The ocular surface · 2023Review
- Prolonged Inflammation and Infectious Changes in the Corneal Epithelium Are Associated with Persistent Epithelial Defect (PED).Pathogens (Basel, Switzerland) · 2023Article
- Flavokawain B Weakens Gastric Cancer Progression via the TGF-Journal of immunology research · 2022Article
- 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
- 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
- Corneal epithelial development and homeostasis.Differentiation; research in biological diversityReview
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Purpose: Krüppel-like factor 4 (KLF4) promotes corneal epithelial (CE) cell fate while suppressing mesenchymal properties. TGF-β plays a crucial role in cell differentiation and development, and if dysregulated, it induces epithelial-mesenchymal transition (EMT). As KLF4 and TGF-β regulate each other in a context-dependent manner, we evaluated the role of the crosstalk between KLF4 and TGF-β-signaling in CE homeostasis. Methods: We used spatiotemporally regulated ablation of Klf4 within the adult mouse CE in ternary transgenic Klf4Δ/ΔCE (Klf4LoxP/LoxP/ Krt12rtTA/rtTA/ Tet-O-Cre) mice and short hairpin RNA (shRNA)-mediated knockdown or lentiviral vector-mediated overexpression of KLF4 in human corneal limbal epithelial (HCLE) cells to evaluate the crosstalk between KLF4 and TGF-β-signaling components. Expression of TGF-β signaling components and cyclin-dependent kinase (CDK) inhibitors was quantified by quantitative PCR, immunoblots, and/or immunofluorescent staining. Results: CE-specific ablation of Klf4 resulted in (1) upregulation of TGF-β1, -β2, -βR1, and -βR2; (2) downregulation of inhibitory Smad7; (3) hyperphosphorylation of Smad2/3; (4) elevated nuclear localization of phospho-Smad2/3 and Smad4; and (5) downregulation of CDK inhibitors p16 and p27. Consistently, shRNA-mediated knockdown of KLF4 in HCLE cells resulted in upregulation of TGF-β1 and -β2, hyperphosphorylation and nuclear localization of SMAD2/3, downregulation of SMAD7, and elevated SMAD4 nuclear localization. Furthermore, overexpression of KLF4 in HCLE cells resulted in downregulation of TGF-β1, -βR1, and -βR2 and upregulation of SMAD7, p16, and p27. Conclusions: Collectively, these results demonstrate that KLF4 regulates CE cell cycle progression by suppressing canonical TGF-β signaling and overcomes the undesirable concomitant decrease in TGF-β-dependent CDK inhibitors p16 and p27 expression by directly upregulating them.
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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.