Evidence map›Paper›PMID 28549095›Full record

ArticleInvestigative ophthalmology & visual science2017

KLF4 Plays an Essential Role in Corneal Epithelial Homeostasis by Promoting Epithelial Cell Fate and Suppressing Epithelial-Mesenchymal Transition.

Anil Tiwari, Chelsea L Loughner, Sudha Swamynathan, Shivalingappa K Swamynathan

Open access · goldAbstract read
In one paragraph

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 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
1.9field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. Pooled it
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  12. ETS1-HMGA2 Axis Promotes Human Limbal Epithelial Stem Cell Proliferation.Investigative ophthalmology & visual science · 2023
    Article
  13. Frontiers in immunology · 2023
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Anil TiwariDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
Chelsea L LoughnerDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
Sudha SwamynathanDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
Shivalingappa K SwamynathanDepartment of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States 2McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States 3Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States 4Fox Center for Vision Restoration, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States.
University of Pittsburgh · US

Funding

Virus Production and Manipulation of Protein/Gene Expression ModuleP30EY008098 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Yuanyuan Chen · 1989 to 2026
$17.8M
Ocular Surface Functions of KLF4 and KLF5R01EY026533 · NEI · UNIVERSITY OF SOUTH FLORIDA · PI SWAMYNATHAN, SHIVALINGAPPA KOTTUR · 2016 to 2025
$3.4M
NEI NIH HHS P30 EY008098NEI NIH HHS R01 EY026533
6 · The paper itself

Abstract

Purpose: The purpose of this study was to test the hypothesis that KLF4 promotes corneal epithelial (CE) cell fate by suppressing the epithelial-mesenchymal transition (EMT), using spatiotemporally regulated CE-specific ablation of Klf4 in Klf4Δ/ΔCE (Klf4LoxP/LoxP/Krt12rtTA/rtTA/Tet-O-Cre) mice. Methods: CE-specific ablation of Klf4 was achieved by feeding Klf4Δ/ΔCE mice with doxycycline chow. The wild-type (WT; normal chow-fed littermates) and the Klf4Δ/ΔCE histology was compared by hematoxylin and eosin-stained sections; EMT marker expression was quantified by quantitative PCR, immunoblots, and immunofluorescent staining; and wound healing rate was measured by CE debridement using Algerbrush. KLF4 and EMT markers were quantified in human corneal limbal epithelial (HCLE) cells undergoing TGF-β1-induced EMT by quantitative PCR, immunoblots, and immunofluorescent staining. Results: The epithelial markers E-cadherin, Krt12, claudin-3, and claudin-4 were down-regulated, whereas the mesenchymal markers vimentin, β-catenin, survivin, and cyclin-D1 and the EMT transcription factors Snail, Slug, Twist1, Twist2, Zeb1, and Zeb2 were up-regulated in the Klf4Δ/ΔCE corneas. The Klf4Δ/ΔCE cells migrated faster, filling 93% of the debrided area within 16 hours compared with 61% in the WT. After 7 days of wounding, the Klf4Δ/ΔCE cells that filled the gap failed to regain epithelial characteristics, as they displayed abnormal stratification; down-regulation of E-cadherin and Krt12; up-regulation of β-catenin, survivin, and cyclin-D1; and a 2.5-fold increase in the number of proliferative Ki67+ cells. WT CE cells at the migrating edge and the HCLE cells undergoing TGF-β1-induced EMT displayed significant down-regulation of KLF4. Conclusions: Collectively, these results reveal that KLF4 plays an essential role in CE homeostasis by promoting epithelial cell fate and suppressing EMT.

Indexed as

AnimalsBiomarkersCell DifferentiationDown-RegulationEpithelial CellsEpithelial-Mesenchymal TransitionEpithelium, CornealHomeostasisHumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceReal-Time Polymerase Chain ReactionTranscription FactorsUp-RegulationBiomarkersKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsTranscription Factors

Identifiers

PMID28549095
PMCPMC5455171
OpenAlexW2617439846

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.