RRC ID 68960
Author Nanba D, Toki F, Asakawa K, Matsumura H, Shiraishi K, Sayama K, Matsuzaki K, Toki H, Nishimura EK.
Title EGFR-mediated epidermal stem cell motility drives skin regeneration through COL17A1 proteolysis.
Journal J Cell Biol
Abstract Skin regenerative capacity declines with age, but the underlying mechanisms are largely unknown. Here we demonstrate a functional link between epidermal growth factor receptor (EGFR) signaling and type XVII collagen (COL17A1) proteolysis on age-associated alteration of keratinocyte stem cell dynamics in skin regeneration. Live-imaging and computer simulation experiments predicted that human keratinocyte stem cell motility is coupled with self-renewal and epidermal regeneration. Receptor tyrosine kinase array identified the age-associated decline of EGFR signaling in mouse skin wound healing. Culture experiments proved that EGFR activation drives human keratinocyte stem cell motility with increase of COL17A1 by inhibiting its proteolysis through the secretion of tissue inhibitor of metalloproteinases 1 (TIMP1). Intriguingly, COL17A1 directly regulated keratinocyte stem cell motility and collective cell migration by coordinating actin and keratin filament networks. We conclude that EGFR-COL17A1 axis-mediated keratinocyte stem cell motility drives epidermal regeneration, which provides a novel therapeutic approach for age-associated impaired skin regeneration.
Volume 220(11)
Published 2021-11-1
DOI 10.1083/jcb.202012073
PII 212656
PMID 34550317
PMC PMC8563287
MeSH 3T3 Cells Animals Autoantigens / metabolism* Cell Line Cell Movement / physiology* Epidermal Cells / metabolism Epidermal Growth Factor / metabolism ErbB Receptors / metabolism Hair Follicle / metabolism Humans Keratinocytes / metabolism Male Mice Mice, Inbred C57BL Non-Fibrillar Collagens / metabolism* Proteolysis Regeneration / physiology* Signal Transduction / physiology Skin / metabolism* Stem Cells / metabolism Wound Healing / physiology
IF 8.811
DNA material CSII-CMV-MCS (RDB04377) pCMV-VSV-G-RSV-Rev (RDB04393) pCAG-HIVgp (RDB04394)