Expression of Raf Kinase Inhibitor Protein in Keratinocyte Differentiation in the Mouse Epidermis

Raf kinase inhibitor protein (RKIP) has been demonstrated to bind to Raf-1 and mitogen-activated protein kinase kinase (MEK) and to inhibit the mitogen-activated protein kinase (MAPK) signaling pathway. Recently, we have discovered that introduction of the RKIP gene into human keratinocytes induces differentiation. In this study, we first examined expression of RKIP in the mouse epidermis in vivo and found that RKIP was expressed in all keratinocyte layers. However, western blot analysis clearly showed that differentiated keratinocytes expressed more RKIP than undifferentiated keratinocytes. These data indicated that RKIP expression in the mouse epidermis increased with keratinocyte differentiation. As 1 ,25-dihydoxyvitamin D3 (1,25(OH)2D3) suppresses keratinocyte proliferation and promotes differentiation, we next examined the effect of 1,25 (OH)2D3 on RKIP expression and found that 1,25(OH)2D3 increased mRNA and protein expression of RKIP in cultured mouse keratinocytes. These results suggest that 1,25 (OH)2D3-induced keratinocyte differentiation may be mediated by induction of RKIP expression. Hirosaki Med.J. 62:166―172,2011