TRPV6 Is a Ca2 Entry Channel Essential for Ca2-induced

Ca2 is an essential factor inducing keratinocyte differentia-tion due to the natural Ca2 gradient in the skin. However, the membrane mechanisms that mediate calcium entry and trigger keratinocyte differentiation had not previously been elucidated. In this study we demonstrate that Ca2-induced differentiation up-regulates both mRNA and protein expression of a transient receptor potential highly Ca2-selective channel, TRPV6. The latter mediates Ca2 uptake and accounts for the basal [Ca2]i in human keratinocytes. Our results show that TRPV6 is a pre-requisite for keratinocyte entry into differentiation, because the silencing of TRPV6 in human primary keratinocytes led to the development of impaired differentiated phenotype triggered by Ca2. The expression of such differentiationmarkers as involu-crin, transglutaminase-1, and cytokeratin-10 was significantly inhibited by small interfering RNA-TRPV6 as compared wit