Effects of sphingoid bases on the sphingolipidome in early keratinocyte differentiation

Abstract

Keratinocyte sphingolipids are structural elements of epidermal permeability barrier and potential regulators of epidermal functions. We tested the influence of sphingoid bases sphinganine, sphingosine and phytosphingosine on in vitro keratinocyte differentiation. Lipidomic and transcriptomic analysis after treatment emphasizes sphinganine and phytosphingosine as potent modulators of keratinocyte differentiation and lipid metabolism. Sphinganine treatment regulated differentiation and sphingolipid metabolism-related genes, and also increased all major ceramide species. Sphingosine treatment increased ceramide and phytoceramide pools without changes in dihydroceramides. Phytosphingosine treatment markedly increased phytoceramide pools without raising ceramide or dihydroceramide levels. Sphinganine treatment increased specifically very long chain ceramides essential for intact barrier function. In summary, sphingoid bases, especially sphinganine, promote differentiation and ceramide production in keratinocytes. Free sphinganine may serve as a dermatological and cosmetic agent by enhancing formation and maintenance of an intact epidermal lipid barrier, with beneficial effects for skin and hair care applications.Abbreviations: FA, fatty acid; SpB, sphingoid base.

Phytosphingosine Increases Biosynthesis of Phytoceramide by Uniquely Stimulating the Expression of Dihydroceramide C4‐desaturase (DES2) in Cultured Human Keratinocytes

“…As reported by other groups, we confirmed that ceramide NP species markedly increased in cultured KC upon the treatment of PHS by the HPTLC analysis, which is consistent with the previous reports (Sigruener et al, ). In Fig.…”

“…Our previous study showed that PHS enhanced both biosynthesis and degradation pathways of filaggrin, which eventually resulted in increasing the natural moisturizing factor (NMF) in human skin (Choi et al, ). Recently, Sigruener et al reported that all three sphingoids, SPH, DHS, and PHS, showed strong regulatory effects on genes involved in KC differentiation and CER biosynthesis (Sigruener et al, ). Particularly, they claimed that DHS stimulated general biosynthetic processes of all different CER in SC.…”

Molecular mechanism for sphingosine-induced Pseudomonas ceramidase expression through the transcriptional regulator SphR

“…demonstrated that Sph produced by the action of CerN is converted to S1P and induces production of inflammatory mediators in human keratinocytes46. In addition, exogenous Sph, dihydroSph, and phytoSph are found to be modulators of differentiation and lipid metabolism in keratinocytes4748. These observations indicate that CerN disturbs the skin barrier function by decreasing the levels of skin Cer and by increasing the long-chain bases.…”

Role of Sphingolipids in Non-melanoma Skin Cancer

“…A recent study by Paragh et al [ 80 ] demonstrated that DHS also promotes the differentiation of keratinocytes. Finally, Sigruener et al [ 81 ] demonstrated that treatment with PHS and DHS increase the levels of phytoceramides and very long-chain ceramides, respectively and leads to the differentiation of keratinocytes. Collectively, this suggests that either sphingoid bases, phytoceramides, and/or ceramides mediate keratinocyte differentiation.…”