Evidence map›Paper›PMID 32042069›Full record

ArticleScientific reports2020

Endoplasmic reticulum stress promotes inflammation-mediated proteolytic activity at the ocular surface.

Ashley M Woodward, Antonio Di Zazzo, Stefano Bonini, Pablo Argüeso

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

25 citing papers in PubMed, 32 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Challenges and advances in ocular mucous membrane pemphigoid (OMMP); from pathogenesis to treatment strategies.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2025
    Review
  8. Rekindling Vision: Innovative Strategies for Treating Retinal Degeneration.International journal of molecular sciences · 2025
    Review
  9. Review
  10. Article
  11. Cysteinyl Leukotriene Receptor Antagonism by Montelukast to Treat Visual Deficits.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. 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 2 institutions in 2 countries.

Ashley M WoodwardSchepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States.
Antonio Di ZazzoOphthalmology Complex Unit, Campus Bio-Medico University of Rome, Rome, Italy.
Stefano BoniniOphthalmology Complex Unit, Campus Bio-Medico University of Rome, Rome, Italy.
Pablo ArgüesoSchepens Eye Research Institute of Massachusetts Eye and Ear, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States. pablo_argueso@meei.harvard.edu.
Harvard University · USUniversità Campus Bio-Medico · IT

Funding

VISION RESEARCHP30EY003790 · NEI · SCHEPENS EYE RESEARCH INSTITUTE · PI Patricia Ann D'Amore · 1985 to 2026
$25.5M
N-Glycosylation and Ocular Surface HomeostasisR01EY026147 · NEI · TUFTS MEDICAL CENTER · PI Pablo Argueso · 2016 to 2026
$5.1M
NEI NIH HHS P30 EY003790NEI NIH HHS R01 EY026147NEI NIH HHS R01EY026147
6 · The paper itself

Abstract

A growing body of evidence implicates endoplasmic reticulum (ER) stress in the pathogenesis of chronic inflammatory and autoimmune disorders. Here, we demonstrate that the proinflammatory cytokine TNFα stimulates matrix metalloproteinase 9 (MMP9) at the ocular surface through a c-Fos-dependent mechanism of ER stress. We found positive reactivity of the molecular chaperone BiP/GRP78 in conjunctival epithelium of patients with ocular cicatricial pemphigoid and increased levels of BiP/GRP78, sXBP1 and GRP94 in human corneal epithelial cells treated with TNFα. Pharmacological blockade of ER stress in vitro using dexamethasone or the chemical chaperones TUDCA and 4PBA attenuated MMP9 expression and secretion in the presence of TNFα. Moreover, expression analysis of genes associated with inflammation and autoimmunity identified the c-Fos proto-oncogene as a mediator of ER stress responses in epithelial cells. Substantially less TNFα-induced MMP9 expression occurred when c-Fos signaling was suppressed with a function-blocking antibody. Taken together, these results indicate that activation of ER stress contributes to promote inflammation-mediated proteolytic activity and uncovers a target for restoring tissue homeostasis in ocular autoimmune disease.

Indexed as

AdultAgedAged, 80 and overAutoimmune DiseasesCase-Control StudiesCell LineConjunctivaEndoplasmic Reticulum Chaperone BiPEndoplasmic Reticulum StressEpithelial CellsFemaleHeat-Shock ProteinsHumansMaleMatrix Metalloproteinase 9Membrane GlycoproteinsEndoplasmic Reticulum Chaperone BiPendoplasminFOS protein, humanHeat-Shock ProteinsHSPA5 protein, humanMAS1 protein, humanMatrix Metalloproteinase 9Membrane GlycoproteinsMMP9 protein, humanProto-Oncogene MasProto-Oncogene Proteins c-fosTNF protein, humanTumor Necrosis Factor-alphaX-Box Binding Protein 1XBP1 protein, human

Identifiers

PMID32042069
PMCPMC7010695
OpenAlexW3005446714

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.