DNA and Cell Biology, 2019. 38(9), 905-914, DOI: https://doi.org/10.1089/dna.2018.4557

Global DNA Methylation Pattern of Fibroblasts in Idiopathic Pulmonary Fibrosis

Jong-Uk Lee, Ji-Hye Son;Eun-Young Shim;Hyun Sub Cheong;Seung-Woo Shin;Hyoung Doo Shin;Ae Rin Baek;Seongho Ryu;Choon-Sik Park;Hun Soo Chang;Jong-Sook Park

Abstract

Our previous tranome study of cultured fibroblasts identified 178 genes that were differentially expressedby 8 idiopathic pulmonary fibrosis (IPF) fibroblasts compared with 4 controls. Here, we performed genomewideDNA methylation analysis to evaluate the relationship of CpG methylation to differential gene expression.Among 485,577 loci, 5850 loci on 2282 genes showed significant differences between the 2 groups (delta-beta>10.21 and p-value <0.05). Among these, beta values of 80 CpGs (30 hypermethylated and 50 hypomethylated)were significantly correlated with mRNA expression of 34 genes (19.1%) of the 178 differentially expressedgenes between the 2 groups (13 downregulated and 21 upregulated). Gene ontology enrichment of these genesincluded cell adhesion, molecule binding, chemical homeostasis, surfactant homeostasis, and receptor binding.One-third of them are involved in the known process of fibrosis; the others are novel genes with respect topulmonary fibrosis. We identified relationships between the altered DNA methylation levels and about one-fifthof the corresponding changes in gene expression by lung tissue fibroblasts. Findings from this study providenew information on novel genes responsible for the pathogenesis of IPF under the control of CpG methylationchanges in IPF lungs.

• DOI: https://doi.org/10.1089/dna.2018.4557
• ISBN or ISSN: 1044-5498

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.