Chondroitin 6-sulfate represses keratinocyte proliferation in mouse skin, which is associated with psoriasis

Commun Biol. 2021 Jan 25;4(1):114. doi: 10.1038/s42003-020-01618-5.

Abstract

Chondroitin sulfates are implicated in epidermal biology, but functional significance of chondroitin sulfates remains unclear. Here, we report that chondroitin 6-sulfate is important for the maintenance of epidermal homeostasis. Mice deficient in chondroitin 6-O-sulfotransferase-1 (C6st-1), which is involved in biosynthesis of chondroitin 6-sulfate, exhibited keratinocyte hyperproliferation and impaired skin permeability barrier function. Chondroitin 6-sulfate directly interacted with the EGF receptor and negatively controlled ligand-induced EGF receptor signaling. Normal function of hyperproliferative C6st-1-knockout mouse-derived keratinocytes was rescued by treatment with exogenous chondroitin 6-sulfate. Epidermal hyperplasia, induced using imiquimod, was more severe in C6st-1-knockout mice than in C6st-1 wild-type mice. Taken together, these findings indicate that chondroitin 6-sulfate represses keratinocyte proliferation in normal skin, and that the expression level of C6st-1 may be associated with susceptibility to psoriasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbohydrate Sulfotransferases
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Chondroitin Sulfates / metabolism
  • Chondroitin Sulfates / pharmacology*
  • Epidermis / drug effects
  • Epidermis / physiology
  • Genetic Predisposition to Disease
  • HaCaT Cells
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / physiology
  • Mice
  • Mice, Knockout
  • Psoriasis* / genetics
  • Psoriasis* / metabolism
  • Psoriasis* / pathology
  • Skin / cytology
  • Skin / drug effects
  • Sulfotransferases / genetics
  • Sulfotransferases / metabolism

Substances

  • Chondroitin Sulfates
  • Sulfotransferases