Intercellular and intracellular functions of ceramides and their metabolites in skin (Review)

The skin consists of the epidermis, dermis and subcutis. The epidermis is primarily comprised of keratinocytes and is separated into four layers according to the stage of differentiation of the keratinocytes. Corneocytes are terminally differentiated keratinocytes that closely interact with other corneocytes through corneodesmosomes, and synthesize lamellar bodies and the intercellular multilamellar barrier, which protects the body from the external environment. As ceramides are the principal components of lamellar bodies and the multilamellar barrier, it is important to understand the biosynthesis of ceramides and their functions in skin. Ceramides are synthesized by amide bond-mediated interactions between sphingoid bases, long-chain amino alcohols [long-chain base] and fatty acids through a de novo pathway, a sphingomyelin (SM) hydrolysis pathway and a catabolic pathway. The majority of ceramides produced by the de novo pathway form the epidermal barrier. Ceramides used as signaling molecules are synthesized by the SM and catabolic pathways. Synthesized ceramides are released from corneocytes and form the multilamellar barrier. Additionally, ceramides and their metabolites regulate the apoptosis, proliferation and differentiation of skin cells as well as the formation of the skin barrier. Thus, the study of ceramides and their metabolites is crucial to understanding the function and regulation of the skin barrier.