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Global methylation patterns in idiopathic pulmonary fibrosis

UNSPECIFIED (2012) Global methylation patterns in idiopathic pulmonary fibrosis. PLoS ONE, 7 (4).

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Abstract

Background: Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessive extracellular matrix deposition, myofibroblast foci, alveolar epithelial cell hyperplasia and extensive remodeling. The role of epigenetic changes in determining the lung phenotype in IPF is unknown. In this study we determine whether IPF lungs exhibit an altered global methylation profile. Methodology/Principal Findings: Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs was hybridized to Agilent human CpG Islands Microarrays and data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages. Array results were validated using the EpiTYPER MassARRAY platform for 3 CpG islands. 625 CpG islands were differentially methylated between IPF and control lungs with an estimated False Discovery Rate less than 5%. The genes associated with the differentially methylated CpG islands are involved in regulation of apoptosis, morphogenesis and cellular biosynthetic processes. The expression of three genes (STK17B, STK3 and HIST1H2AH) with hypomethylated promoters was increased in IPF lungs. Comparison of IPF methylation patterns to lung cancer or control samples, revealed that IPF lungs display an intermediate methylation profile, partly similar to lung cancer and partly similar to control with 402 differentially methylated CpG islands overlapping between IPF and cancer. Despite their similarity to cancer, IPF lungs did not exhibit hypomethylation of long interspersed nuclear element 1 (LINE-1) retrotransposon while lung cancer samples did, suggesting that the global hypomethylation observed in cancer was not typical of IPF. Conclusions/Significance: Our results provide evidence that epigenetic changes in IPF are widespread and potentially important. The partial similarity to cancer may signify similar pathogenetic mechanisms while the differences constitute IPF or cancer specific changes. Elucidating the role of these specific changes will potentially allow better understanding of the pathogenesis of IPF. © 2012 Rabinovich et al.


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Details

Item Type: Article
Status: Published
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorEickelberg, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Date: 10 April 2012
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 7
Number: 4
DOI or Unique Handle: 10.1371/journal.pone.0033770
Schools and Programs: School of Medicine > Critical Care Medicine
Refereed: Yes
Other ID: NLM PMC3323629
PubMed Central ID: PMC3323629
PubMed ID: 22506007
Date Deposited: 24 Sep 2012 20:03
Last Modified: 08 Jan 2019 07:55
URI: http://d-scholarship.pitt.edu/id/eprint/14169

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