Evidence map›Paper›PMID 27010479›Full record

ArticlePloS one2016

Methylation Microarray Studies Highlight PDGFA Expression as a Factor in Biliary Atresia.

Zenobia C Cofer, Shuang Cui, Steven F EauClaire, Cecilia Kim, John W Tobias, Hakon Hakonarson, Kathleen M Loomes, Randolph P Matthews

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
3.5field-weighted citation impact, top 8% 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

17 citing papers in PubMed, 30 citations in OpenAlex.

  1. Biliary atresia-related liver fibrosis.Frontiers in cell and developmental biology · 2026
    Review
  2. Review
  3. Article
  4. Genetic background and biliary atresia.World journal of pediatric surgery · 2025
    Review
  5. Article
  6. Biliary atresia.Nature reviews. Disease primers · 2024
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Observational
  13. Article
  14. Zebrafish as a Model to Study Cholestatic Liver Diseases.Methods in molecular biology (Clifton, N.J.) · 2019
    Article
  15. Clinical epigenetics · 2018
    Article
  16. Article
  17. 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

8 authors at 2 institutions in 1 country.

Zenobia C CoferDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States of America.
Shuang CuiDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States of America.
Steven F EauClaireDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States of America.
Cecilia KimCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
John W TobiasPenn Center for Biomedical Informatics, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
Hakon HakonarsonCenter for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States of America.
Kathleen M LoomesDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States of America.
Randolph P MatthewsDivision of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia Research Institute, Philadelphia, Pennsylvania, United States of America.
Children's Hospital of Philadelphia · USUniversity of Pennsylvania · US

Funding

DNA methylation in biliary development and diseaseR01DK090260 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI LOOMES, KATHLEEN MARY, SPINNER, NANCY BETTINA · 2011 to 2015
$2.1M
NIDDK NIH HHS R01 DK090260NIDDK NIH HHS R01DK090260
6 · The paper itself

Abstract

Biliary atresia (BA) is a progressive fibro-inflammatory disorder that is the leading indication for liver transplantation in children. Although there is evidence implicating genetic, infectious, environmental, and inflammatory causes, the etiology of BA remains unknown. We have recently reported that cholangiocytes from BA patients showed decreased DNA methylation relative to disease- and non-disease controls, supporting a potential role for DNA hypomethylation in BA etiopathogenesis. In the current study, we examined the methylation status of specific genes in human BA livers using methylation microarray technology. We found global DNA hypomethylation in BA samples as compared to disease- and non-disease controls at specific genetic loci. Hedgehog pathway members, SHH and GLI2, known to be upregulated in BA, were both hypomethylated, validating this approach as an investigative tool. Another region near the PDGFA locus was the most significantly hypomethylated in BA, suggesting potential aberrant expression. Validation assays confirmed increased transcriptional and protein expression of PDGFA in BA livers. We also show that PDGF-A protein is specifically localized to cholangiocytes in human liver samples. Injection of PDGF-AA protein dimer into zebrafish larvae caused biliary developmental and functional defects. In addition, activation of the Hedgehog pathway caused increased expression of PDGF-A in zebrafish larvae, providing a previously unrecognized link between PDGF and the Hedgehog pathway. Our findings implicate DNA hypomethylation as a specific factor in mediating overexpression of genes associated with BA and identify PDGF as a new candidate in BA pathogenesis.

Indexed as

DNA MethylationGene Expression RegulationAnimalsBile DuctsBiliary AtresiaGenetic LociHedgehog ProteinsHumansKruppel-Like Transcription FactorsLiverNuclear ProteinsPlatelet-Derived Growth FactorUp-RegulationZebrafishZinc Finger Protein Gli2GLI2 protein, humanHedgehog ProteinsKruppel-Like Transcription FactorsNuclear ProteinsPlatelet-Derived Growth Factorplatelet-derived growth factor ASHH protein, humanZinc Finger Protein Gli2

Identifiers

PMID27010479
PMCPMC4806872
OpenAlexW2332174551

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.