SOX2 Epidermal Overexpression Promotes Cutaneous Wound Healing via Activation of EGFR/MEK/ERK Signaling Mediated by EGFR Ligands.
Animals
Cell Proliferation
/ genetics
Cells, Cultured
ErbB Receptors
/ metabolism
Female
Heparin-binding EGF-like Growth Factor
/ genetics
Keratinocytes
/ metabolism
Ligands
MAP Kinase Signaling System
/ genetics
Male
Mice
Models, Animal
Primary Cell Culture
RNA-Seq
SOXB1 Transcription Factors
/ genetics
Signal Transduction
/ genetics
Skin
/ cytology
Up-Regulation
Wound Healing
/ genetics
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:
08 2019
08 2019
Historique:
received:
11
10
2018
revised:
09
01
2019
accepted:
01
02
2019
pubmed:
18
2
2019
medline:
2
6
2020
entrez:
18
2
2019
Statut:
ppublish
Résumé
Oral mucosa contains a unique transcriptional network that primes oral wounds for rapid resolution in humans. Our previous work identified genes that were consistently upregulated in the oral mucosa and demonstrated that induction of one of the identified genes, transcription factor SOX2, promoted cutaneous wound healing in mice. In this study, we investigated the molecular and cellular mechanisms by which SOX2 accelerates wound healing in skin. RNA-sequencing analysis showed that SOX2 induced a proliferative and wound-activated phenotype in skin keratinocytes prior to wounding. During wound healing, SOX2 induced proliferation of epithelial and connective tissue cells and promoted angiogenesis. Chromatin immunoprecipitation assay revealed that SOX2 directly regulates expression of EGFR ligands, resulting in activation of EGFR. In vitro, skin keratinocytes overexpressing SOX2 promoted cell migration via the EGFR/MEK/ERK pathway. We conclude that induction of SOX2 in skin keratinocytes accelerates cutaneous wound healing by promoting keratinocyte migration and proliferation, and enhancement of angiogenesis via upregulation of EGFR ligands and activation of EGFR/MEK/ERK pathway. Through the identification of putative cutaneous SOX2 targets, such as HBEGF, this study opens venues to determine clinical targets for treatment of skin wounds.
Identifiants
pubmed: 30772301
pii: S0022-202X(19)30116-2
doi: 10.1016/j.jid.2019.02.004
pmc: PMC6650375
mid: NIHMS1521682
pii:
doi:
Substances chimiques
Hbegf protein, mouse
0
Heparin-binding EGF-like Growth Factor
0
Ligands
0
SOXB1 Transcription Factors
0
Sox2 protein, mouse
0
EGFR protein, mouse
EC 2.7.10.1
ErbB Receptors
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1809-1820.e8Subventions
Organisme : NCI NIH HHS
ID : R33 CA225291
Pays : United States
Organisme : Intramural NIH HHS
ID : Z01 AR041124-09
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA AR041124
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.
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