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A methylome and transcriptome analysis of normal human scar cells reveals a role for FOXF2 in scar maintenance


Stevenson, AW and Melton, PE and Moses, EK and Wallace, HJ and Wood, FM and Rea, S and Danielsen, PL and Alghamdi, M and Hortin, N and Borowczyk, J and Deng, Z and Manzur, M and Fear, MW, A methylome and transcriptome analysis of normal human scar cells reveals a role for FOXF2 in scar maintenance, The Journal of Investigative Dermatology pp. 1-22. ISSN 0022-202X (2021) [Refereed Article]

Copyright Statement

Copyright 2021 The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology

DOI: doi:10.1016/j.jid.2021.08.445


Scars are maintained for life and increase in size during periods of growth such as puberty. Epigenetic changes in fibroblasts after injury may underpin the maintenance and growth of scars. In this study, we combined methylome and transcriptome data from normotrophic mature scar and contralateral uninjured normal skin fibroblasts to identify potential regulators of scar maintenance. In total, 219 significantly differentially expressed and 1,199 significantly differentially methylated promoters were identified, of which there were 12 genes both significantly differentially methylated and expressed. Of these, the two transcription factors, FOXF2 and MKX, were selected for further analysis. Immunocytochemistry and qPCR suggested that FOXF2 but not MKX had elevated expression in scar fibroblasts. Using RNA sequencing, FOXF2 knockdown was shown to significantly reduce the expression of extracellular matrix‒related genes, whereas MKX did not appear to affect similar pathways. Finally, FOXF2 knockdown was also shown to significantly decrease collagen I production in scar and keloid fibroblasts. This study provides insights into the maintenance of normotrophic scar, suggesting that FOXF2 is an important regulator of this process. Targeting genes responsible for maintenance of scar phenotype may ameliorate scar appearance and improve patient outcomes in the future.

Item Details

Item Type:Refereed Article
Keywords:scars, wound healing, DNA methylation, RNA-Seq, FOXF2, MKX
Research Division:Biological Sciences
Research Group:Bioinformatics and computational biology
Research Field:Genomics and transcriptomics
Objective Division:Health
Objective Group:Evaluation of health and support services
Objective Field:Determinants of health
UTAS Author:Melton, PE (Dr Phillip Melton)
UTAS Author:Moses, EK (Professor Eric Moses)
ID Code:148678
Year Published:2021
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-02-02
Last Modified:2022-08-19

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