Evidence map›Paper›PMID 31013745›Full record

ArticleCells2019

YAP, ΔNp63, and β-Catenin Signaling Pathways Are Involved in the Modulation of Corneal Epithelial Stem Cell Phenotype Induced by Substrate Stiffness.

Ricardo M Gouveia, Flora Vajda, Jason A Wibowo, Francisco Figueiredo, Che J Connon

Open access · goldAbstract read
In one paragraph

Article in Cells, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
5.3field-weighted citation impact, top 4% 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

39 citing papers in PubMed, 57 citations in OpenAlex.

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  19. Hyaluronan Modulates the Biomechanical Properties of the Cornea.Investigative ophthalmology & visual science · 2022
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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

5 authors at 1 institution in 1 country.

Ricardo M GouveiaInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne NE1 3BZ, UK. ricardo.gouveia@newcastle.ac.uk.ORCID 0000-0002-2968-1298
Flora VajdaInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne NE1 3BZ, UK. vajdaflo@gmail.com.
Jason A WibowoInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne NE1 3BZ, UK. jasonowo.anthony@hotmail.com.
Francisco FigueiredoInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne NE1 3BZ, UK. francisco.figueiredo@newcastle.ac.uk.
Che J ConnonInstitute of Genetic Medicine, Newcastle University, International Centre for Life, Newcastle-upon-Tyne NE1 3BZ, UK. che.connon@newcastle.ac.uk.
Centre for Life · GB

Funding

Department of Health PB-PG-1215-20037Medical Research Council G0900879Medical Research Council MR/K017217/1Medical Research Council MR/K017217/2Medical Research Council MR/S035826/1
6 · The paper itself

Abstract

Recent studies have established that the phenotype of epithelial stem cells residing in the corneal periphery (the limbus) depends on this niche's distinct biomechanical properties. However, the signaling pathways underlying this dependency are still poorly understood. To address this issue, we investigated the effect of substrate stiffness on the migration, proliferation, and molecular phenotype of human limbal epithelial stem cells (LESCs). Specifically, we demonstrated that cells grown on collagen-based substrates with limbus-like compliance showed higher proliferation and stratification and lower migration capabilities, as well as higher levels of pro-proliferative markers Ki67 and β-Catenin, and LESC markers ΔNp63, ABCG2, and CK15. In contrast, cells on stiffer substrates lost these stem/progenitor cell markers, but instead expressed the key mechanotransduction factor YAP, as well as elevated levels of BMP4, a promotor of cell differentiation known to be negatively regulated by Wnt/β-Catenin signaling. This data allowed us to propose a new model that integrates the various molecular pathways involved in LESC response to substrate stiffness. This model will potentially be a useful guide to future research on the mechanisms underlying LESC loss following fibrosis-causing injuries.

Indexed as

Adaptor Proteins, Signal TransducingAgedbeta CateninCell DifferentiationCell ProliferationCorneaCorneal DiseasesEpithelial CellsEpitheliumEpithelium, CornealFemaleHumansLimbus CorneaeMaleMechanotransduction, CellularPhenotypeAdaptor Proteins, Signal Transducingbeta CateninTP63 protein, humanTranscription FactorsTumor Suppressor ProteinsYAP1 protein, humanYAP-Signaling Proteinsepithelial stratificationfibrosislimbal epithelial stem cellsmechanotransductiontissue stiffnessβ-Catenin signaling

Identifiers

PMID31013745
PMCPMC6523807
OpenAlexW2937617045

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.