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Glucosylceramides stimulate murine epidermal hyperproliferation

N L Marsh1, P M Elias, W M Holleran

  • 1Dermatology Service, Department of Veterans Affairs Medical Center, San Francisco, California 94121, USA.

The Journal of Clinical Investigation
|June 1, 1995
PubMed
Summary
This summary is machine-generated.

Glucosylceramides (GlcCer) stimulate epidermal cell proliferation, contrary to the growth-inhibiting effects of ceramides. This study shows GlcCer directly promotes skin cell growth and hyperplasia.

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Area of Science:

  • Biochemistry
  • Dermatology
  • Cell Biology

Background:

  • Beta-glucocerebrosidase hydrolyzes glucosylceramides (GlcCer) into ceramides, vital for skin barrier function.
  • Ceramides regulate cell proliferation and differentiation, often acting as growth inhibitors.
  • GlcCer has been suggested to have mitogenic properties, contrasting with ceramides.

Purpose of the Study:

  • To investigate if increased GlcCer levels stimulate epidermal cell proliferation (mitogenesis).
  • To examine the effects of both endogenous and exogenous GlcCer on hairless mouse epidermis.

Main Methods:

  • Topical application of conduritol B epoxide, a beta-glucocerebrosidase inhibitor, to increase epidermal GlcCer.
  • Intracutaneous administration of GlcCer.
  • Measurement of [3H]thymidine incorporation to assess DNA synthesis and proliferation.
  • Autoradiography to localize proliferation within skin layers.
  • Evaluation of epidermal permeability and assessment for irritant effects.

Main Results:

  • Inhibiting beta-glucocerebrosidase significantly increased epidermal GlcCer levels, particularly in the basal proliferative layer.
  • This increase in GlcCer correlated with a significant stimulation of epidermal proliferation and hyperplasia.
  • Direct administration of GlcCer also enhanced epidermal DNA synthesis.
  • Combined treatment showed additive effects on DNA synthesis.
  • Proliferation increases were not due to altered skin barrier function or irritation.

Conclusions:

  • Glucosylceramides (GlcCer) directly stimulate epidermal cell proliferation.
  • GlcCer acts as a mitogen in the epidermis, promoting cell growth and hyperplasia.
  • Findings suggest a novel role for GlcCer in regulating skin cell growth beyond its role as a ceramide precursor.