Evidence map›Paper›PMID 18556592›Full record

ArticleAmerican journal of respiratory cell and molecular biology2008

Thy-1 promoter hypermethylation: a novel epigenetic pathogenic mechanism in pulmonary fibrosis.

Yan Y Sanders, Annie Pardo, Moisés Selman, Gerard J Nuovo, Trygve O Tollefsbol, Gene P Siegal, James S Hagood

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory cell and molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
128citing papers in PubMed, 1 pooled it
4.3field-weighted citation impact, top 5% 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

128 citing papers in PubMed, 1 synthesis or guideline pooled it, 237 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Review
  6. Pharmacological mechanism of active components inFrontiers in pharmacology · 2026
    Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Review
  12. DNA methylation modification in Idiopathic pulmonary fibrosis.Frontiers in cell and developmental biology · 2024
    Review
  13. Article
  14. Review
  15. Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023
    Review
  16. Review
  17. Article
  18. Article
  19. DNA methylation in pulmonary fibrosis and lung cancer.Expert review of respiratory medicine · 2022
    Review
  20. Review

68 more citing papers are in PubMed but not listed here.

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 4 institutions in 2 countries.

Yan Y SandersDepartment of Pediatrics, Division of Pulmonary Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Annie Pardo
Moisés Selman
Gerard J Nuovo
Trygve O Tollefsbol
Gene P Siegal
James S Hagood
University of Alabama at Birmingham · USInstituto Nacional de Enfermedades Respiratorias · MXThe Ohio State University · USUniversidad Nacional Autónoma de México · MX

Funding

Regulation of Fibroblast Phenotype in Lung FibrosisR01HL082818 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAGOOD, JAMES S. · 2007 to 2017
$3.7M
EXTRAMURAL RESEARCH FACILITIES CONTRUCTIONC06RR015490 · NCRR · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI GERRITY, LAURETTA W · 2000 to 2000
$1.0M
NCRR NIH HHS C06 RR15490NHLBI NIH HHS R01 HL082818
6 · The paper itself

Abstract

Mechanisms regulating myofibroblastic differentiation of fibroblasts within fibroblastic foci in idiopathic pulmonary fibrosis (IPF) remain unclear. Epigenetic processes, including DNA methylation, produce heritable but potentially reversible changes in DNA or its associated proteins and are prominent in development and oncogenesis. We have shown that Thy-1 suppresses myofibroblastic differentiation of lung fibroblasts and that fibroblasts in fibroblastic foci are Thy-1(-). Epigenetic down-regulation of Thy-1 has been demonstrated in cellular transformation and clinical cancer. We hypothesized that epigenetic regulation of Thy-1 affects the lung fibroblast fibrogenic phenotype. RT-PCR, methylation-specific PCR (MSP), and bisulfite genomic sequencing were used to determine the methylation status of the Thy-1 promoter in Thy-1(+) and Thy-1(-) lung fibroblasts, and MSP-in situ hybridization (MSPISH) was performed on fibrotic tissue. Thy-1 gene expression is absent in Thy-1(-) human and rat fibroblasts despite intact Thy-1 genomic DNA. Cytosine-guanine islands in the Thy-1 gene promoter are hypermethylated in Thy-1(-), but not Thy-1(+), fibroblasts. RT-PCR and MSP demonstrate that, in IPF samples in which Thy-1 expression is absent, the Thy-1 promoter region is methylated, whereas in lung samples retaining Thy-1 expression, the promoter region is unmethylated. MSPISH confirms methylation of the Thy-1 promoter in fibroblastic foci in IPF. Treatment with DNA methyltransferase inhibitors restores Thy-1 expression in Thy-1(-) fibroblasts. Epigenetic regulation of Thy-1 is a novel and potentially reversible mechanism in fibrosis that may offer the possibility of new therapeutic options.

Indexed as

DNA MethylationAnimalsCells, CulturedDNA Modification MethylasesEpigenesis, GeneticFibroblastsGene Expression RegulationGenome, HumanHumansImmunohistochemistryPromoter Regions, GeneticProtein BindingPulmonary FibrosisRatsRNA, MessengerThy-1 AntigensDNA Modification MethylasesRNA, MessengerThy-1 Antigens

Identifiers

PMID18556592
PMCPMC2574530
OpenAlexW2073763489

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.