Evidence map›Paper›PMID 29947284›Full record

ArticleInhalation toxicology

Acute inhalation of ozone induces DNA methylation of apelin in lungs of Long-Evans rats.

Colette N Miller, Janice A Dye, Mette C Schladweiler, Judy H Richards, Allen D Ledbetter, Erica J Stewart, Urmila P Kodavanti

Abstract read
In one paragraph

Article in Inhalation toxicology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.7field-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

14 citing papers in PubMed, 23 citations in OpenAlex.

  1. Review
  2. Skeletal Muscle as Endocrine Organ.Advances in experimental medicine and biology · 2025
    Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Apelin/APJ system: an emerging therapeutic target for respiratory diseases.Cellular and molecular life sciences : CMLS · 2020
    Review
  11. Review
  12. Article
  13. Ozone Exposure During Implantation Increases Serum Bioactivity in HTR-8/SVneo Trophoblasts.Toxicological sciences : an official journal of the Society of Toxicology · 2019
    Article
  14. 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 2 institutions in 1 country.

Colette N Millera Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Cardiopulmonary and Immunology Branch, Office of Research and Development , US Environmental Protection Agency , Research Triangle Park , NC , USA.ORCID 0000-0001-7599-7886
Janice A Dyea Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Cardiopulmonary and Immunology Branch, Office of Research and Development , US Environmental Protection Agency , Research Triangle Park , NC , USA.ORCID 0000-0002-4220-2490
Mette C Schladweilera Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Cardiopulmonary and Immunology Branch, Office of Research and Development , US Environmental Protection Agency , Research Triangle Park , NC , USA.
Judy H Richardsa Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Cardiopulmonary and Immunology Branch, Office of Research and Development , US Environmental Protection Agency , Research Triangle Park , NC , USA.
Allen D Ledbettera Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Cardiopulmonary and Immunology Branch, Office of Research and Development , US Environmental Protection Agency , Research Triangle Park , NC , USA.
Erica J Stewartb Oak Ridge Institute for Science and Education , Oak Ridge , TN , USA.
Urmila P Kodavantia Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, Cardiopulmonary and Immunology Branch, Office of Research and Development , US Environmental Protection Agency , Research Triangle Park , NC , USA.ORCID 0000-0001-6333-1024
Environmental Protection Agency · USOak Ridge Associated Universities · US

Funding

Intramural EPA EPA999999
6 · The paper itself

Abstract

Apelin has cardiopulmonary protective properties that promote vasodilation and maintenance of the endothelial barrier. While reductions in apelin have been identified as a contributor to various lung diseases, including pulmonary edema, its role in the effect of air pollutants has not been examined. Thus, in the current study, we sought to investigate if apelin is a downstream target of inhaled ozone and if such change in expression is related to altered DNA methylation in the lung. Male, Long-Evans rats were exposed to filtered air or 1.0 ppm ozone for 4 h. Ventilation changes were assessed using whole-body plethysmography immediately following exposure, and markers of pulmonary edema and inflammation were assessed in the bronchoaveolar lavage (BAL) fluid. The enzymatic regulators of DNA methylation were measured in the lung, along with methylation and hydroxymethylation of the apelin promoter. Data showed that ozone exposure was associated with increased enhanced pause and protein leakage in the BAL fluid. Ozone exposure reduced DNA cytosine-5-methyltransferase (DNMT) activity and Dnmt3a/b gene expression. Exposure-induced upregulation of proliferating cell nuclear antigen, indicative of DNA damage, repair, and maintenance methylation. Increased methylation and reduced hydroxymethylation were measured on the apelin promoter. These epigenetic modifications accompanied ozone-induced reduction of apelin expression and development of pulmonary edema. In conclusion, epigenetic regulation, specifically increased methylation of the apelin promoter downstream of DNA damage, may lead to reductions in protective signaling of the apelinergic system, contributing to the pulmonary edema observed following the exposure to oxidant air pollution.

Indexed as

DNA DamageInhalation ExposureAnimalsApelinCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA Methyltransferase 3BEpigenesis, GeneticLungMaleOzoneProliferating Cell Nuclear AntigenPromoter Regions, GeneticPulmonary EdemaApelinApln protein, ratDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNA Methyltransferase 3BOzoneProliferating Cell Nuclear AntigenApelinDNA methylationozonepulmonary edema

Identifiers

PMID29947284
PMCPMC6681647
OpenAlexW2811007465

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.