EGFR-mediated Epidermal Stem Cell Motility Drives Skin Regeneration Through COL17A1 Proteolysis

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2021 Sep 22

PMID 34550317

Citations 19

Authors

Daisuke Nanba

Fujio Toki

Kyosuke Asakawa

Hiroyuki Matsumura

Ken Shiraishi

Koji Sayama

Kyoichi Matsuzaki

Hiroshi Toki

Emi K Nishimura

Affiliations

Soon will be listed here.

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.

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