Decreased expression of GPC1 in human skin keratinocytes and epidermis during ageing

Exp Gerontol. 2019 Oct 15:126:110693. doi: 10.1016/j.exger.2019.110693. Epub 2019 Aug 17.

Abstract

Background: Glypicans (GPCs) are heparan sulfate cell membrane proteoglycans containing glycosylphosphatidylinositol (GPI) anchor. They play important role in cell behavior by activating/presenting numerous growth factors and cytokines.

Objectives: The expression of GPCs was investigated in primary culture of skin keratinocytes sampled from healthy donors of different age.

Materials and methods: Primary keratinocytes from healthy female donors aged from 20 to 89 years old (n = 30) were either isolated from breast or abdominal skin samples (n = 27) or purchased (n = 3). GPCs expression was examined by qPCR, immunohistochemistry and western blot. Its role in proliferation induced by fibroblast growth factor 2 (FGF2) was also studied.

Results: Glypican 1 (GPC1) was the major expressed GPC in human keratinocytes. Its expression was up to two orders of magnitude higher than other GPCs and was significantly decreased with the age of the donors. It was localized at the cell surface and associated with intracellular granules. In skin sections, GPC1 was mainly localized in basal layer of epidermis. Shedding of GPCs decreased the proliferative effect of FGF2, confirming their role of modulator of growth factor effects on keratinocytes. These results established GPC1 as an important player in epidermis biology and skin ageing.

Keywords: Ageing; Epidermis; Glypican 1; Human skin; Keratinocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / metabolism*
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Epidermis / metabolism
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Gene Expression Regulation / physiology
  • Glypicans / genetics
  • Glypicans / metabolism*
  • Humans
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism*
  • Middle Aged
  • RNA, Messenger / genetics
  • Signal Transduction / physiology
  • Skin / metabolism*
  • Young Adult

Substances

  • GPC1 protein, human
  • Glypicans
  • RNA, Messenger
  • Fibroblast Growth Factor 2