Novel sphingolipid derivatives promote keratinocyte differentiation

György Paragh, Petra Schling, Peter Ugocsai, Alexander E. Kel, Gerhard Liebisch, Susanne Heimerl, Christoph Moehle, Yvonne Schiemann, Michael Wegmann, Mike Farwick, Norbert M. Wikonkál, József Mandl, Thomas Langmann, Gerd Schmitz

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17 Citations (Scopus)

Abstract

Sphingolipids are important components of the water permeability barrier of the skin. Moreover, ceramides were also shown to influence keratinocyte differentiation and regulate cellular signalling. A confluence-induced differentiation model of normal human keratinocytes was established to allow evaluation of pro- and anti-differentiation effects of exogenous compounds. The effects of phytosphingosine (PS), sphingosine (SO), sphinganine (SA) and their hexanoyl (-C6), stearoyl (-C18) and salicyl (-SLC) derivatives, C12-alkylamine-salicylate (C12-SLC), salicylate (SLC) along with vitamin D3 (VD3) and retinol as control substances were tested in this system. Cytotoxicity assays were carried out to optimize the incubation conditions of compounds and whole genome expression changes were monitored by DNA-microarray on days 0, 1 and 4. Geometric means of gene expression levels of a subset of known keratinocyte differentiation-related genes were calculated from the microarray data to compare effects of the sphingolipid derivatives. Compound treatment-induced transcriptional changes were analysed by the ExPlain™ software (BIOBASE GmbH). Five of the assayed substances (SA, SO-C6, PS-C6, SO-SLC, PS-SLC) were found to be potent promoters of keratinocyte differentiation compared with VD3, and C12-SLC revealed potential anti-differentiation properties. ExPlain™ analysis found a different regulatory profile in the computed transcriptional networks of the sphingoid bases versus their -C6 and especially -SLC derivatives suggesting that the change in their keratinocyte differentiation modifying potential is due to a unique effect of the covalent attachment of the salicylic acid. Taken together, these results demonstrate the gene regulatory potential of sphingolipid species that could be valuable for dermatological or cosmetic applications.

Original languageEnglish
Pages (from-to)1004-1016
Number of pages13
JournalExperimental Dermatology
Volume17
Issue number12
DOIs
Publication statusPublished - Nov 24 2008

Keywords

  • Ceramides
  • Microarray
  • NHEK
  • Promoter analysis
  • Salicylic acid

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology

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  • Cite this

    Paragh, G., Schling, P., Ugocsai, P., Kel, A. E., Liebisch, G., Heimerl, S., Moehle, C., Schiemann, Y., Wegmann, M., Farwick, M., Wikonkál, N. M., Mandl, J., Langmann, T., & Schmitz, G. (2008). Novel sphingolipid derivatives promote keratinocyte differentiation. Experimental Dermatology, 17(12), 1004-1016. https://doi.org/10.1111/j.1600-0625.2008.00736.x