Paragh, Gyoergy and Schling, Petra and Ugocsai, Peter and Kel, Alexander E. and Liebisch, Gerhard and Heimerl, Susanne and Moehle, Christoph and Schiemann, Yvonne and Wegmann, Michael and Farwick, Mike and Wikonkal, Norbert M. and Mandl, Jozsef and Langmann, Thomas and Schmitz, Gerd (2008) Novel sphingolipid derivatives promote keratinocyte differentiation. EXPERIMENTAL DERMATOLOGY, 17 (12). pp. 1004-1016. ISSN 0906-6705, 1600-0625
Full text not available from this repository. (Request a copy)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 (TM) 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 (TM) 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CULTURED HUMAN KERATINOCYTES; EPIDERMAL BARRIER FUNCTION; COMPOSITE REGULATORY ELEMENTS; BINDING SITE COMBINATIONS; STRATUM-CORNEUM; TERMINAL DIFFERENTIATION; TRANSCRIPTION FACTORS; LIPID ENVELOPE; MODULE ANALYST; HUMAN SKIN; ceramides; microarray; NHEK; promoter analysis; salicylic acid |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Oct 2020 10:07 |
| Last Modified: | 14 Oct 2020 10:07 |
| URI: | https://pred.uni-regensburg.de/id/eprint/29956 |
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