Development of a new model of reconstituted mouse epidermis and characterization of its response to proinflammatory cytokines

J Tissue Eng Regen Med. 2018 Feb;12(2):e1098-e1107. doi: 10.1002/term.2442. Epub 2017 Jun 26.

Abstract

The development of three-dimensional models of reconstituted mouse epidermis (RME) has been hampered by the difficulty to maintain murine primary keratinocyte cultures and to achieve a complete epidermal stratification. In this study, a new protocol is proposed for the rapid and convenient generation of RME, which reproduces accurately the architecture of a normal mouse epidermis. During RME morphogenesis, the expression of differentiation markers such as keratins, loricrin, filaggrin, E-cadherin and connexins was followed, showing that RME structure at day 5 was similar to those of a normal mouse epidermis, with the acquisition of the natural barrier function. It was also demonstrated that RME responded to skin-relevant proinflammatory cytokines by increasing the expression of antimicrobial peptides and chemokines, and inhibiting epidermal differentiation markers, as in the human system. This new model of RME is therefore suitable to investigate mouse epidermis physiology further and opens new perspectives to generate reconstituted epidermis from transgenic mice.

Keywords: cytokine; keratinocyte; reconstituted epidermis; skin inflammation; three-dimensional culture.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / drug effects
  • Adherens Junctions / metabolism
  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Cell Differentiation / drug effects
  • Cytokines / toxicity*
  • Epidermis / drug effects*
  • Filaggrin Proteins
  • Gap Junctions / drug effects
  • Gap Junctions / metabolism
  • Inflammation Mediators / toxicity*
  • Mice, Inbred C57BL
  • Models, Biological*
  • Morphogenesis / drug effects
  • Receptors, Cytokine / metabolism

Substances

  • Biomarkers
  • Cytokines
  • FLG protein, human
  • Filaggrin Proteins
  • Inflammation Mediators
  • Receptors, Cytokine