Evidence map›Paper›PMID 35802384›Full record

ArticleInvestigative ophthalmology & visual science2022

Integrated Stress Response Regulation of Corneal Epithelial Cell Motility and Cytokine Production.

Hsiao-Sang Chu, Cornelia Peterson, Xitiz Chamling, Cynthia Berlinicke, Donald Zack, Albert S Jun, James Foster

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Investigative ophthalmology & visual science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 50% 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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
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

7 authors at 3 institutions in 2 countries.

Hsiao-Sang ChuDepartment of Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan.
Cornelia PetersonDepartment of Molecular and Comparative Pathology, Johns Hopkins School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
Xitiz ChamlingDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
Cynthia BerlinickeDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
Donald ZackDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
Albert S JunDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
James FosterDepartment of Ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States.
Johns Hopkins Medicine · USJohns Hopkins University · USNational Taiwan University · TW

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
Training Veterinarians for Careers in Biomedical ResearchT32OD011089 · OD · JOHNS HOPKINS UNIVERSITY · PI JOSEPH L MANKOWSKI · 2012 to 2026
$6.7M
NEI NIH HHS P30 EY001765NIH HHS T32 OD011089
6 · The paper itself

Abstract

Purpose: To investigate the effect of an active integrated stress response (ISR) on human corneal epithelial cell motility and cytokine production. Methods: ISR agonists tunicamycin (TUN) and SAL003 (SAL) were used to stimulate the ISR in immortalized corneal epithelial cell lines, primary human limbal epithelial stem cells, and ex vivo human corneas. Reporter lines for ISR-associated transcription factors activating transcription factor 4 (ATF4) and XBP1 activity were generated to visualize pathway activity in response to kinase-specific agonists. Scratch assays and multiplex magnetic bead arrays were used to investigate the effects of an active ISR on scratch wounds and cytokine production. A C/EBP homologous protein (CHOP) knockout cell line was generated to investigate the effects of ISR ablation. Finally, an ISR antagonist was assayed for its ability to rescue negative phenotypic changes associated with an active ISR. Results: ISR stimulation, mediated through CHOP, inhibited cell motility in both immortalized and primary human limbal epithelial cells. Scratch wounding of ex vivo corneas elicited an increase in the ISR mediators phosphorylated-eIF2α and ATF4. ISR stimulation also increased the production of vascular endothelial growth factor (VEGF) and proinflammatory cytokines. ISR ablation, through CHOP knockout or inhibition with integrated stress response inhibitor (ISRIB) rescued epithelia migration ability and reduced VEGF secretion. Conclusions: We demonstrate that the ISR has dramatic effects on the ability of corneal epithelial cells to respond to wounding models and increases the production of proinflammatory and angiogenic factors. Inhibition of the ISR may provide a new therapeutic option for corneal diseases in which the ISR is implicated.

Indexed as

Stress, PhysiologicalVascular Endothelial Growth Factor AActivating Transcription Factor 4CytokinesEpithelial CellsHumansActivating Transcription Factor 4CytokinesVascular Endothelial Growth Factor A

Identifiers

PMID35802384
PMCPMC9279922
OpenAlexW4284962648

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.