Abstract
The epidermal barrier function requires optimal keratinocyte differentiation and epidermal lipid synthesis. Liver X receptor (LXR) α and β, are important transcriptional regulators of the epidermal gene expression. Here, we show that raffinose, a ubiquitously present trisaccharide in plants, activated the transcriptional activity of LXRα/β, which led to the induction of genes required for keratinocyte differentiation such as involucrin and filaggrin, and genes involved in lipid metabolism and transport including SCD1 and ABCA1 in both HaCaT and normal human epidermal keratinocytes. Raffinose induced the expression of JunD and Fra1, and their DNA binding in the AP1 motif in the promoters of involucrin and loricrin. Interestingly, LXR bound the AP1 motif upon raffinose treatment, and conversely, JunD and Fra1 bound the LXR response element in promoters of LXR target genes, which indicates the presence of a postive cross-talk between LXR and AP1 in the regualtion of these genes. Finally, the effect of raffinose in epidermal barrier function was confirmed by applying raffinose in an ointment formulation to the skin of hairless mice. These findings suggest that raffinose could be examined as an ingredient in functional cosmetics and therapeutic agents for the treatment of cutaneous disorders associated with abnormal epidermal barrier function.
Highlights
The epidermal barrier function requires optimal keratinocyte differentiation and epidermal lipid synthesis
JunD and Fra[1] increased the TO901317-induced transcriptional function of both LXRαand LXRβin a dose-dependent manner (Supplementary Fig. S6). These results suggested that AP1 that induced by raffinose binds to LXRE or AP1 motif together with liver X receptors (LXRs), and increased transcription of genes those are required for keratinocyte differentiation including LXRα,involucrine, and loricrine (Fig. 5d)
We found a newly identified mechanism of raffinose action in epidermis that activates an activation loop of LXR and AP1 to increase the expression of genes required for keratinocyte differentiation
Summary
The epidermal barrier function requires optimal keratinocyte differentiation and epidermal lipid synthesis. The epidermal barrier is constantly regenerated from differentiating keratinocytes, and abnormalities in this process are associated with a variety of skin diseases such as ichthyosis, psoriasis, and atopic dermatitis[1,3,5] Both keratinocyte differentiation and epidermal lipid synthesis are regulated by several nuclear receptors including retinoic acid receptors, peroxisome proliferator-activated receptors (PPARs), and liver X receptors (LXRs)[6,7]. The LXR-induced epidermal function is accompanied by increased expression of genes involved in both early differentiation (e.g., involucrin) and late differentiation (e.g., loricrin, filaggrin, and transglutaminase (1) This increased gene expression is regulated by the activating protein 1 (AP1) family proteins in normal human epidermal keratinocytes www.nature.com/scientificreports/. We report that raffinose activated transcriptional activity of LXR enhances epidermal barrier function through induction of genes such as involucrin, filaggrin, and AQP3
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
