A Methylome and Transcriptome Analysis of Normal Human Scar Cells Reveals a Role for FOXF2 in Scar Maintenance.
J Invest Dermatol
; 142(5): 1489-1498.e12, 2022 05.
Article
en En
| MEDLINE
| ID: mdl-34687743
ABSTRACT
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 matrixârelated 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cicatriz Hipertrófica
/
Queloide
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Invest Dermatol
Año:
2022
Tipo del documento:
Article