Identification of Differentially Methylated CpG Sites in Fibroblasts from Keloid Scars

被引：16

作者：

Alghamdi, Mansour A. ^{[1
,2
]}

Wallace, Hilary J. ^{[3
,4
]}

Melton, Phillip E. ^{[5
,6
]}

Moses, Eric K. ^{[5
,6
]}

Stevenson, Andrew ^{[4
]}

Al-Eitan, Laith N. ^{[7
,8
]}

Rea, Suzanne ^{[9
,10
]}

Duke, Janine M. ^{[4
]}

Danielsen, Patricia L. ^{[11
,12
]}

Prele, Cecilia M. ^{[13
]}

Wood, Fiona M. ^{[4
,9
,10
,14
]}

Fear, Mark W. ^{[4
,15
]}

机构：

[1] King Khalid Univ, Dept Anat, Coll Med, Abha 61421, Saudi Arabia

[2] King Khalid Univ, Coll Med, Genom & Personalized Med Unit, Abha 61421, Saudi Arabia

[3] Univ Notre Dame Australia, Sch Med, Fremantle, WA 6959, Australia

[4] Univ Western Australia, Sch Biomed Sci, Fac Hlth & Med Sci, Burn Injury Res Unit, Perth, WA 6009, Australia

[5] Univ Western Australia, Fac Hlth & Med Sci, Ctr Genet Origins Hlth & Dis, Perth, WA 6009, Australia

[6] Curtin Univ, Sch Pharm & Biomed Sci, Fac Hlth Sci, Bentley, WA 6102, Australia

[7] Jordan Univ Sci & Technol, Dept Appl Biol Sci, Irbid 22110, Jordan

[8] Jordan Univ Sci & Technol, Dept Biotechnol & Genet Engn, Irbid 22110, Jordan

[9] Perth Childrens Hosp, Burns Serv Western Australia, Perth, WA 6009, Australia

[10] Fiona Stanley Hosp, Dept Hlth, Perth, WA 6009, Australia

[11] Copenhagen Univ Hosp, Dept Dermatol, DK-2400 Copenhagen NV, Denmark

[12] Copenhagen Univ Hosp, Copenhagen Wound Healing Ctr, DK-2400 Copenhagen NV, Denmark

[13] Univ Western Australia, Inst Resp Hlth, Fac Hlth & Med Sci, Perth, WA 6009, Australia

[14] Fiona Wood Fdn, Perth, WA 6150, Australia

[15] Univ Western Australia, Burn Injury Res Unit, M318,35 Stirling Highway, Crawley, WA 6009, Australia

来源：

BIOMEDICINES | 2020年 / 8卷 / 07期

关键词：

keloid scars; DNA methylation; wound healing; epigenetics; NEMO-LIKE KINASE; NANCE-HORAN-SYNDROME; DNA METHYLATION; EPIGENETIC REGULATION; HYPERTROPHIC SCARS; HISTONE CHAPERONE; REMOVES H2A.Z; WIDE ANALYSIS; GENE; ASSOCIATION;

D O I：

10.3390/biomedicines8070181

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 withTNKS2,FAM45B,LOC723972,GAS7,RHBDD2andCAMKK1. 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, andNHSshowed 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.

引用

页数：16

共 102 条

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