Evidence map›Paper›PMID 28606794›Full record

ArticleThe American journal of pathology2017

Antifibrotic Actions of Peroxisome Proliferator-Activated Receptor γ Ligands in Corneal Fibroblasts Are Mediated by β-Catenin-Regulated Pathways.

Kye-Im Jeon, Richard P Phipps, Patricia J Sime, Krystel R Huxlin

Open access · bronzeAbstract read
In one paragraph

Article in The American journal of pathology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

18 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  6. Review
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  11. Review
  12. Article
  13. The Potential Use of Cannabis in Tissue Fibrosis.Frontiers in cell and developmental biology · 2021
    Review
  14. Article
  15. Article
  16. Review
  17. Cryptotanshinone Ameliorates Radiation-Induced Lung Injury in Rats.Evidence-based complementary and alternative medicine : eCAM · 2019
    Article
  18. 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.

Kye-Im JeonFlaum Eye Institute, University of Rochester, Rochester, New York.
Richard P PhippsFlaum Eye Institute, University of Rochester, Rochester, New York; Department of Medicine, University of Rochester, Rochester, New York; Department of Environmental Medicine, University of Rochester, Rochester, New York.
Patricia J SimeDepartment of Medicine, University of Rochester, Rochester, New York; Department of Environmental Medicine, University of Rochester, Rochester, New York.
Krystel R HuxlinFlaum Eye Institute, University of Rochester, Rochester, New York; Center for Visual Science, University of Rochester, Rochester, New York. Electronic address: huxlin@cvs.rochester.edu.
University of Rochester · US

Funding

VISUAL SCIENCE RESEARCH CTR SUPPORTP30EY001319 · NEI · UNIVERSITY OF ROCHESTER · PI Susana Marcos · 1985 to 2026
$17.5M
The role of PPAR{gamma} ligands in corneal wound healing and opticsR01EY015836 · NEI · UNIVERSITY OF ROCHESTER · PI HUXLIN, KRYSTEL R · 2004 to 2023
$7.1M
Aryl Hydrocarbon Receptor Ligands and Thyroid Eye DiseaseR01EY023239 · NEI · UNIVERSITY OF ROCHESTER · PI PHIPPS, RICHARD P. · 2013 to 2016
$1.4M
NEI NIH HHS P30 EY001319NEI NIH HHS R01 EY015836NEI NIH HHS R01 EY023239
6 · The paper itself

Abstract

Wound healing after corneal injury typically involves fibrosis, with transforming growth factor β1 (TGF-β1) as one of its strongest mediators. A class of small molecules-peroxisome proliferator-activated receptor γ (PPARγ) ligands-exert potent antifibrotic effects in the cornea by blocking phosphorylation of p38 mitogen-activated protein kinase (MAPK). However, why this blocks fibrosis remains unknown. Herein, we show that PPARγ ligands (rosiglitazone, troglitazone, and 15-deoxy-Δ12,14-prostaglandin J2) decrease levels of β-catenin. We also show that β-catenin siRNA and the Wingless/integrated (Wnt) inhibitor pyrvinium block the ability of corneal fibroblasts to up-regulate synthesis of α-smooth muscle actin (α-SMA), collagen 1 (COL1), and fibronectin (FN) in response to TGF-β1. Activation of TGF-β receptors and p38 MAPK increased glycogen synthase kinase 3β (GSK3β) phosphorylation, whereas a chemical inhibitor of p38 MAPK (SB203580) reduced the phosphorylation of GSK3β, decreasing active β-catenin levels in both cytoplasmic and nuclear fractions. Finally, lithium chloride, a GSK3 inhibitor, also attenuated the TGF-β1-induced increase in α-SMA, COL1, and FN expression. All in all, our results suggest that TGF-β1 stimulation increases active β-catenin concentration in cultured corneal fibroblasts through p38 MAPK regulation of canonical Wnt/β-catenin signaling, increasing α-SMA, COL1, and FN synthesis. Thus, PPARγ ligands, by blocking TGF-β1-induced p38 MAPK phosphorylation, prevent increases in both total and active β-catenin through p38 MAPK-GSK3β signaling.

Indexed as

ActinsAnimalsbeta CateninCatsChromansCollagen Type ICorneaFibroblastsFibronectinsFibrosisGlycogen Synthase Kinase 3 betaLithium Chloridep38 Mitogen-Activated Protein KinasesPhosphorylationPPAR gammaProstaglandin D215-deoxy-delta(12,14)-prostaglandin J2Actinsbeta CateninChromansCollagen Type IFibronectinsGlycogen Synthase Kinase 3 betaLithium Chloridep38 Mitogen-Activated Protein KinasesPPAR gammaProstaglandin D2pyrviniumPyrvinium CompoundsReceptors, Transforming Growth Factor betaRosiglitazoneThiazolidinedionesTransforming Growth Factor beta1Troglitazone

Identifiers

PMID28606794
PMCPMC5530905
OpenAlexW2622737658

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.