Altered sphingoid base profiles predict compromised membrane structure and permeability in atopic dermatitis.

Background: Ceramide hydrolysis by ceramidase in the stratum corneum (SC) yields both sphingoid bases and free fatty acids (FFA). While FFA are key constituents of the lamellar bilayers that mediate the epidermal permeability barrier, whether sphingoid bases influence permeability barrier homeostasis remains unknown. Pertinently, alterations of lipid profile, including ceramide and ceramidase activities occur in atopic dermatitis (AD).

Vitamin D receptor and coactivators SRC2 and 3 regulate epidermis-specific sphingolipid production and permeability barrier formation.

The vitamin D receptor (VDR) is a nuclear hormone receptor that controls transcription of target genes. It exerts its biological effects through transcriptional coactivators. Previously, we identified two distinct classes of VDR coactivators, VDR-interacting protein (DRIP) and steroid receptor coactivator (SRC) at different stages of keratinocyte differentiation.