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Citations to this article

Glucosylceramides stimulate murine epidermal hyperproliferation.
N L Marsh, … , P M Elias, W M Holleran
N L Marsh, … , P M Elias, W M Holleran
Published June 1, 1995
Citation Information: J Clin Invest. 1995;95(6):2903-2909. https://doi.org/10.1172/JCI117997.
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Research Article

Glucosylceramides stimulate murine epidermal hyperproliferation.

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Abstract

Hydrolysis of glucosylceramides (GlcCer) by beta-glucocerebrosidase generates ceramides, critical components of the epidermal permeability barrier. Ceramides also are involved in the regulation of cellular proliferation and differentiation in a variety of cell types. Whereas most studies have focused on ceramides and their sphingoid base metabolites as growth inhibitors, GlcCer apparently acts oppositely (i.e., as a mitogen). To determine whether enhancement of GlcCer content stimulates epidermal mitogenesis, we examined the response of hairless mouse epidermis to alterations in endogenous and/or exogenous GlcCer. Topical applications of conduritol B epoxide, a specific irreversible inhibitor of beta-glucocerebrosidase, increased epidermal GlcCer levels twofold, an alteration localized largely to the basal, proliferative cell layer (fourfold increase); and stimulated epidermal proliferation (2.3-fold elevation in [3H]thymidine incorporation; P < or = 0.001), localized autoradiographically again to the basal layer, and resulting in epidermal hyperplasia. Intracutaneous administration of GlcCer (2.0 mg) also stimulated epidermal DNA synthesis, while simultaneous treatment with conduritol B epoxide plus GlcCer resulted in an additive increase in DNA synthesis. These increases in epidermal proliferation could not be attributed either to altered epidermal permeability barrier function, or to nonspecific irritant effects, as determined by four separate criteria. These results strongly suggest that GlcCer directly stimulates epidermal mitogenesis.

Authors

N L Marsh, P M Elias, W M Holleran

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Total citations by year

Year: 2022 2021 2020 2019 2018 2016 2015 2014 2013 2012 2011 2010 2009 2008 2006 2005 2004 2003 2002 2001 2000 1999 1998 1997 1996 Total
Citations: 2 2 1 1 1 1 1 2 2 4 2 1 1 2 1 3 1 2 4 2 5 5 7 5 2 60
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