A Methylome and Transcriptome Analysis of Normal Human Scar Cells Reveals a Role for FOXF2 in Scar Maintenance.

Cicatrix, Hypertrophic / pathology Epigenome Fibroblasts / metabolism Forkhead Transcription Factors / genetics Gene Expression Profiling Humans Keloid / pathology

Journal

The Journal of investigative dermatology
ISSN: 1523-1747
Titre abrégé: J Invest Dermatol
Pays: United States
ID NLM: 0426720

Informations de publication

Date de publication:
05 2022
Historique:
received: 11 09 2019
revised: 22 07 2021
accepted: 01 08 2021
pubmed: 24 10 2021
medline: 27 4 2022
entrez: 23 10 2021
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.jid.2021.08.445 PMID: 34687743
pubmed: 34687743
pii: S0022-202X(21)02353-8
doi: 10.1016/j.jid.2021.08.445
pii:
doi:

Substances chimiques

FOXF2 protein, human 0
Forkhead Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1489-1498.e12

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Andrew W Stevenson (AW)

Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia. Electronic address: andrew.stevenson@uwa.edu.au.

Phillip E Melton (PE)

School of Population and Global Health, The University of Western Australia, Perth, Australia; School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Australia; Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia.

Eric K Moses (EK)

School of Pharmacy and Biomedical Sciences, Faculty of Health Sciences, Curtin University, Perth, Australia; Menzies Research Institute, University of Tasmania, Hobart, Tasmania, Australia; School of Biomedical Sciences, University of Western Australia, Crawley, Western Australia, Australia.

Hilary J Wallace (HJ)

Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia; School of Medicine, The University of Notre Dame Australia, Fremantle, Australia.

Fiona M Wood (FM)

Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia; Burns Service of Western Australia, Perth Children's Hospital and Fiona Stanley Hospital, Perth, Australia.

Suzanne Rea (S)

Burns Service of Western Australia, Perth Children's Hospital and Fiona Stanley Hospital, Perth, Australia.

Patricia L Danielsen (PL)

Department of Dermatology and Copenhagen Wound Healing Center, Copenhagen University Hospital, Copenhagen, Denmark.

Mansour Alghamdi (M)

Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia; Genomics and Personalised Medicine Unit, College of Medicine, King Khalid University, Abha, Saudi Arabia.

Nicole Hortin (N)

Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia.

Julia Borowczyk (J)

Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.

Zhenjun Deng (Z)

Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia.

Mitali Manzur (M)

Telethon Kids Institute, Northern Entrance, Perth Children's Hospital, Nedlands, Australia.

Mark W Fear (MW)

Burn Injury Research Unit, School of Biomedical Sciences, Faculty of Health and Medical Sciences, The University of Western Australia, Perth, Australia.

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Classifications MeSH

questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Cicatrice hypertrophique › A Methylome and Transcriptome Analysis of...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Génome › Épigénome › A Methylome and Transcriptome Analysis of...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Fibroblastes › A Methylome and Transcriptome Analysis of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription à motif hélice ailée › Facteurs de transcription Forkhead › A Methylome and Transcriptome Analysis of...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › A Methylome and Transcriptome Analysis of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › A Methylome and Transcriptome Analysis of...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Fibrose › Chéloïde › A Methylome and Transcriptome Analysis of...