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Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung

Huang, Steven K ; Scruggs, Anne M ; McEachin, Richard C ; White, Eric S ; Peters-Golden, Marc Tschumperlin, Daniel J.

PloS one, 2014-09, Vol.9 (9), p.e107055-e107055 [Periódico revisado por pares]

United States: Public Library of Science

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Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung
Autor: Huang, Steven K ; Scruggs, Anne M ; McEachin, Richard C ; White, Eric S ; Peters-Golden, Marc
Tschumperlin, Daniel J.
Assuntos: Adolescent ; Adult ; Aged ; Biology and life sciences ; Biopsy ; Biotechnology ; Bisulfite ; Case-Control Studies ; Cell Line ; Cell lines ; Cell Proliferation ; CpG islands ; CpG Islands - genetics ; Critical care ; Demography ; Deoxyribonucleic acid ; DNA ; DNA methylation ; DNA Methylation - genetics ; DNA sequencing ; Effector cells ; Epigenetics ; Extracellular matrix ; Female ; Fibroblasts ; Fibroblasts - metabolism ; Fibroblasts - pathology ; Fibrosis ; Gas exchange ; Gene expression ; Gene Expression Regulation ; Gene Regulatory Networks ; Gene sequencing ; Gene Silencing ; Genes ; Genome, Human - genetics ; Genomes ; Humans ; Idiopathic Pulmonary Fibrosis - genetics ; Idiopathic Pulmonary Fibrosis - pathology ; Internal medicine ; Ion channels ; Lung - pathology ; Lung diseases ; Lungs ; Male ; Medicine ; Medicine and Health Sciences ; Middle Aged ; Molecular Sequence Annotation ; Morphogenesis ; Pathogenesis ; Patients ; Phenotypes ; Pneumonia ; Potassium ; Potassium channels ; Proteins ; Pulmonary fibrosis ; Respiratory failure ; Young Adult
É parte de: PloS one, 2014-09, Vol.9 (9), p.e107055-e107055
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Conceived and designed the experiments: SKH. Performed the experiments: SKH AMS. Analyzed the data: SKH RCM MPG. Contributed reagents/materials/analysis tools: ESW. Contributed to the writing of the manuscript: SKH RCM MPG.
Competing Interests: The authors have declared that no competing interests exist.
Descrição: Excessive fibroproliferation is a central hallmark of idiopathic pulmonary fibrosis (IPF), a chronic, progressive disorder that results in impaired gas exchange and respiratory failure. Fibroblasts are the key effector cells in IPF, and aberrant expression of multiple genes contributes to their excessive fibroproliferative phenotype. DNA methylation changes are critical to the development of many diseases, but the DNA methylome of IPF fibroblasts has never been characterized. Here, we utilized the HumanMethylation 27 array, which assays the DNA methylation level of 27,568 CpG sites across the genome, to compare the DNA methylation patterns of IPF fibroblasts (n = 6) with those of nonfibrotic patient controls (n = 3) and commercially available normal lung fibroblast cell lines (n = 3). We found that multiple CpG sites across the genome are differentially methylated (as defined by P value less than 0.05 and fold change greater than 2) in IPF fibroblasts compared to fibroblasts from nonfibrotic controls. These methylation differences occurred both in genes recognized to be important in fibroproliferation and extracellular matrix generation, as well as in genes not previously recognized to participate in those processes (including organ morphogenesis and potassium ion channels). We used bisulfite sequencing to independently verify DNA methylation differences in 3 genes (CDKN2B, CARD10, and MGMT); these methylation changes corresponded with differences in gene expression at the mRNA and protein level. These differences in DNA methylation were stable throughout multiple cell passages. DNA methylation differences may thus help to explain a proportion of the differences in gene expression previously observed in studies of IPF fibroblasts. Moreover, significant variability in DNA methylation was observed among individual IPF cell lines, suggesting that differences in DNA methylation may contribute to fibroblast heterogeneity among patients with IPF. These results demonstrate that IPF fibroblasts exhibit global differences in DNA methylation that may contribute to the excessive fibroproliferation associated with this disease.
Editor: United States: Public Library of Science
Idioma: Inglês

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Lung fibroblasts from patients with idiopathic pulmonary fibrosis exhibit genome-wide differences in DNA methylation compared to fibroblasts from nonfibrotic lung

Huang, Steven K ; Scruggs, Anne M ; McEachin, Richard C ; White, Eric S ; Peters-Golden, Marc Tschumperlin, Daniel J.

United States: Public Library of Science

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