Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars
Mansour A. Alghamdi,
Hilary J. Wallace,
Phillip E. Melton,
Eric K. Moses,
Andrew Stevenson,
Laith N. Al-Eitan,
Suzanne Rea,
Janine M. Duke,
Patricia L. Danielsen,
Cecilia M. Prêle,
Fiona M. Wood,
Mark W. Fear
Affiliations
Mansour A. Alghamdi
Department of Anatomy, College of Medicine, King Khalid University, Abha 61421, Saudi Arabia
Hilary J. Wallace
School of Medicine, The University of Notre Dame Australia, Fremantle 6959, Australia
Phillip E. Melton
Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia
Eric K. Moses
Centre for Genetic Origins of Health and Disease, Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia
Andrew Stevenson
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia
Laith N. Al-Eitan
Department of Applied Biological Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan
Suzanne Rea
Burns Service of Western Australia, Perth Children’s Hospital and Fiona Stanley Hospital, Department of Health, Perth 6009, Australia
Janine M. Duke
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia
Patricia L. Danielsen
Department of Dermatology and Copenhagen Wound Healing Center, Copenhagen University Hospital, DK-2400 Copenhagen NV, Denmark
Cecilia M. Prêle
Institute for Respiratory Health, Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia
Fiona M. Wood
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia
Mark W. Fear
Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth 6009, Australia
As a part of an abnormal healing process of dermal injuries and irritation, keloid scars arise on the skin as benign fibroproliferative tumors. Although the etiology of keloid scarring remains unsettled, considerable recent evidence suggested that keloidogenesis may be driven by epigenetic changes, particularly, DNA methylation. Therefore, genome-wide scanning of methylated cytosine-phosphoguanine (CpG) sites in extracted DNA from 12 keloid scar fibroblasts (KF) and 12 control skin fibroblasts (CF) (six normal skin fibroblasts and six normotrophic fibroblasts) was conducted using the Illumina Human Methylation 450K BeadChip in two replicates for each sample. Comparing KF and CF used a Linear Models for Microarray Data (Limma) model revealed 100,000 differentially methylated (DM) CpG sites, 20,695 of which were found to be hypomethylated and 79,305 were hypermethylated. The top DM CpG sites were associated with TNKS2, FAM45B, LOC723972, GAS7, RHBDD2 and CAMKK1. Subsequently, the most functionally enriched genes with the top 100 DM CpG sites were significantly (p ≤ 0.05) associated with SH2 domain binding, regulation of transcription, DNA-templated, nucleus, positive regulation of protein targeting to mitochondrion, nucleoplasm, Swr1 complex, histone exchange, and cellular response to organic substance. In addition, NLK, CAMKK1, LPAR2, CASP1, and NHS showed to be the most common regulators in the signaling network analysis. Taken together, these findings shed light on the methylation status of keloids that could be implicated in the underlying mechanism of keloid scars formation and remission.
