Protein kinase C δ and η differently regulate the expression of loricrin and Jun family proteins in human keratinocytes

Abstract

Barrier function of the epidermis is maintained by precise expression of keratinocyte-specific structural proteins to form the cornified cell envelope (CE). Loricrin, a major component of the CE, is expressed at the late stage of keratinocyte differentiation. In this study, we reveal the isoform-specific function of protein kinase C (PKC) in the regulation of loricrin expression. Both PKCδ and PKCη have been recognized as differentiation-promoting isoforms. However, loricrin expression was inversely controlled by PKCδ and PKCη in cultured keratinocytes and 3D skin culture; i.e. loricrin expression was decreased by PKCδ and increased by PKCη. To clarify the mechanisms that PKCδ and PKCη oppositely regulate the loricrin expression, we examined the expression of activator protein-1 (AP-1) family proteins, which modulate the transcription of loricrin and are downstream molecules of PKC. PKCδ decreased c-Jun expression, whereas PKCη increased JunD, which are positive regulators of loricrin transcription. These findings suggest that inverse effects of PKCδ and PKCη on loricrin expression attributes to the expression of c-Jun and JunD.