Type XVII collagen coordinates proliferation in the interfollicular epidermis

Elife. 2017 Jul 11;6:e26635. doi: 10.7554/eLife.26635.

Abstract

Type XVII collagen (COL17) is a transmembrane protein located at the epidermal basement membrane zone. COL17 deficiency results in premature hair aging phenotypes and in junctional epidermolysis bullosa. Here, we show that COL17 plays a central role in regulating interfollicular epidermis (IFE) proliferation. Loss of COL17 leads to transient IFE hypertrophy in neonatal mice owing to aberrant Wnt signaling. The replenishment of COL17 in the neonatal epidermis of COL17-null mice reverses the proliferative IFE phenotype and the altered Wnt signaling. Physical aging abolishes membranous COL17 in IFE basal cells because of inactive atypical protein kinase C signaling and also induces epidermal hyperproliferation. The overexpression of human COL17 in aged mouse epidermis suppresses IFE hypertrophy. These findings demonstrate that COL17 governs IFE proliferation of neonatal and aged skin in distinct ways. Our study indicates that COL17 could be an important target of anti-aging strategies in the skin.

Keywords: developmental biology; epidermis; extracellular matrix; human; human biology; medicine; mouse; stem cells; tissue homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Cell Proliferation*
  • Epidermis / physiology*
  • Humans
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Non-Fibrillar Collagens / genetics
  • Non-Fibrillar Collagens / metabolism*
  • Wnt Signaling Pathway

Substances

  • Autoantigens
  • Non-Fibrillar Collagens
  • collagen type XVII

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.