Sphingolipid signaling in epidermal homeostasis. Current knowledge and new therapeutic approaches in dermatology

In the present review we have attempted to give an overview of the role of sphingolipids in skin homoeostasis. Sphingolipid metabolites are emerging as potent second messengers in diverse cellular signaling pathways. In the skin little is known about sphingolipids in signaling events. In various cell populations it has been shown that different sphingolipid metabolites have opposing effects on the biological outcome of a stimulus. Therefore, the term 'sphingolipid rheostat' has been established and has also been shown to exist in skin-derived cell populations. In many cells ceramide is a mediator of proliferation inhibition and apoptosis, whereas sphingosine-1-phosphate acts more like a growth factor and reverses ceramide effects. In keratinocytes extracellular and intracellular ceramides play important roles. Extracellular ceramides are necessary for the water retention capacity and for maintaining the permeability barrier of the skin. Intracellular ceramides cause differentiation of keratinocytes. Until now less is known about the effect of other sphingolipid metabolites in the skin.