Evidence map›Paper›PMID 20042643›Full record

ArticleInvestigative ophthalmology & visual science2010

Molecular mechanism of proinflammatory cytokine-mediated squamous metaplasia in human corneal epithelial cells.

Shimin Li, Marianne Gallup, Ying-Ting Chen, Nancy A McNamara

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
4.3field-weighted citation impact, top 6% 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

30 citing papers in PubMed, 62 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Corneal injury repair and the potential involvement of ZEB1.Eye and vision (London, England) · 2024
    Review
  6. Natural killer cells drive 4-1BBL positive uveal melanoma towards EMT and metastatic disease.Journal of experimental & clinical cancer research : CR · 2024
    Article
  7. Article
  8. Effect of TRPM8 Functional Loss on Corneal Epithelial Wound Healing in Mice.Investigative ophthalmology & visual science · 2023
    Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Cannabinoid-induced chemotaxis in bovine corneal epithelial cells.Investigative ophthalmology & visual science · 2015
    Article
  20. 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

4 authors at 1 institution in 1 country.

Shimin LiFrancis I. Proctor Foundation, University of California, San Francisco, CA 94143-0412, USA.
Marianne Gallup
Ying-Ting Chen
Nancy A McNamara
University of California, San Francisco · US

Funding

Rapid-Prototyping and Design CoreP30EY002162 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LAKKARAJU, APARNA · 1985 to 2024
$16.8M
Molecular Mechanisms of Squamous Metaplasia in Dry EyeR01EY016203 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MCNAMARA, NANCY A · 2006 to 2013
$3.2M
NEI NIH HHS EY02162NEI NIH HHS P30 EY002162NEI NIH HHS R01 EY016203NEI NIH HHS R01EY 016203
6 · The paper itself

Abstract

purposeThe cornified envelope protein small proline-rich protein 1B (SPRR1B) is a biomarker for squamous metaplasia. Proinflammatory cytokines IL-1beta and IFN-gamma are potent inducers of ocular surface keratinization and SPRR1B expression. Here the molecular mechanisms controlling SPRR1B gene expression in response to IL-1beta and IFN-gamma are elucidated.

methodsA 3-kb fragment of the SPRR1B gene 5'-flanking region was amplified from human chromosome 1, sequentially deleted, and cloned into a luciferase vector. Constructs were transiently transfected into human corneal epithelial cells, and activity was assessed in response to IL-1beta, IFN-gamma, or basal medium. Functional cis-elements responding to IL-1beta and IFN-gamma were characterized by site-directed mutagenesis and gel mobility shift assay. Effects of mitogen-activated protein kinases p38, ERK, and JNK were assessed using inhibitors and dominant-negative mutants. Results were validated by real-time RT-PCR.

resultsThe first 620 bp of the SPRR1B 5'-flanking region regulated constitutive expression and increased promoter activity in response to IL-1beta and IFN-gamma. Corresponding cis-elements for IL-1beta and IFN-gamma were bound by cAMP response element binding protein (CREB) and zinc-finger E-box binding homeobox 1 (ZEB1), respectively. Inhibition of p38 abolished the stimulatory effects of IL-1beta and IFN-gamma on SPRR1B, whereas inhibition of JNK and ERK had no effect. Dominant-negative mutants targeting p38alpha and p38beta2 blocked cytokine-induced SPRR1B promoter activity and mRNA expression.

conclusionsSPRR1B is upregulated by the proinflammatory cytokines IL-1beta and IFN-gamma via p38 MAPK-mediated signaling pathways that lead to the activation of transcription factors CREB and ZEB1, respectively. These results identify key intracellular signaling intermediates involved in the pathogenesis of immune-mediated ocular surface squamous metaplasia.

Indexed as

Antigens, Polyomavirus TransformingBiomarkersCell Culture TechniquesCell Line, TransformedCorneaCornified Envelope Proline-Rich ProteinsCyclic AMP Response Element-Binding ProteinElectrophoretic Mobility Shift AssayEpithelium, CornealExtracellular Signal-Regulated MAP KinasesGene Expression RegulationHomeodomain ProteinsHumansInterferon-gammaInterleukin-1betaMAP Kinase Kinase 4Antigens, Polyomavirus TransformingBiomarkersCornified Envelope Proline-Rich ProteinsCyclic AMP Response Element-Binding ProteinExtracellular Signal-Regulated MAP KinasesHomeodomain ProteinsInterferon-gammaInterleukin-1betaMAP Kinase Kinase 4p38 Mitogen-Activated Protein KinasesRNA, MessengerSPRR1B protein, humanTranscription FactorsZEB1 protein, humanZinc Finger E-box-Binding Homeobox 1

Identifiers

PMID20042643
PMCPMC2868474
OpenAlexW2080992511

What OpenQuestion holds

Textmetadata
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.