Evidence map›Paper›PMID 40314655›Full record

ArticleInvestigative ophthalmology & visual science2025

Retinoic Acid Receptor Alpha- and Beta-Mediated Signaling Regulates Conjunctival Epithelial Cell Keratinization.

Hokoru Yoshioka, Mayumi Ueta, Seiichi Yokoo, Norihiko Yokoi, Katsura Mizushima, Yuji Naito, Shigeru Kinoshita, Chie Sotozono

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In one paragraph

Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Hokoru YoshiokaDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Mayumi UetaDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Seiichi YokooDepartment of Tissue Engineering, The University of Tokyo Hospital, Tokyo, Japan.
Norihiko YokoiDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Katsura MizushimaDepartment of Human Immunology and Nutrition Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yuji NaitoDepartment of Human Immunology and Nutrition Science, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Shigeru KinoshitaDepartment of Frontier Medical Science and Technology for Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Chie SotozonoDepartment of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: Keratinization of the mucosal epithelia develops in severe ocular surface disorders, causing severe visual loss. This study elucidates the molecular mechanisms of keratinization in conjunctival epithelial cells (CjECs) and investigates the involvement of the vitamin A pathway. Methods: Keratinized conjunctival epithelial sheets were generated by a closed system culture of human CjECs and confirmed by immunostaining. Comprehensive gene expression analysis and quantitative real-time PCR (qRT-PCR) were used to examine whether the cells could be used as an in vitro keratinization model. Moreover, immunostaining and qRT-PCR were used to examine alterations of vitamin A pathway-related genes in the cells and also the effect of adding all-trans retinoic acid (ATRA) and retinoic acid receptor alpha/beta (RARA/RARB) agonist Am80. Knockdown of RARA or RARB was also performed using transfection of small interfering RNA to identify receptors for retinoic acid. Results: Immunostaining revealed that CjECs cultured in a closed system had increased expression of keratinization markers. Comprehensive gene expression analysis and qRT-PCR revealed expression changes in vitamin A pathway genes, in addition to keratinization. In the closed system culture, immunostaining revealed that conjunctival epithelial keratinization was suppressed or partially ameliorated by ATRA or Am80, and qRT-PCR revealed that vitamin A pathway-related genes were significantly altered. Moreover, knockdown of RARA or RARB induced an increase in keratinization marker involucrin. Conclusions: Keratinization of CjECs involves RARA or RARB-mediated pathways, and ATRA and Am80 alter the expression of vitamin A pathway gene and suppress keratinization.

Indexed as

ConjunctivaEpithelial CellsGene Expression RegulationKeratinsReceptors, Retinoic AcidSignal TransductionCells, CulturedHumansReal-Time Polymerase Chain ReactionRetinoic Acid Receptor alphaTretinoinVitamin AKeratinsRARA protein, humanReceptors, Retinoic AcidRetinoic Acid Receptor alpharetinoic acid receptor betaTretinoinVitamin A

Identifiers

PMID40314655
PMCPMC12054659

What Socratic holds

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Registered trials

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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.