恒常的活性化型カルシニューリンによるケラチノサイト増殖抑制と発毛阻害機序

抄録

Calcineurin/NFAT pathway plays important roles in various tissues such as cardiac muscle, neuron and immune systems. Recent studies have shown that the pathway is also involved in keratinocyte growth/differentiation. However, little is known the mechanism in the regulation. In the present study, we showed that a novel splicing variant form of calcineurin A-beta, which was deficient in the auto-inhibitory domain, was predominantly expressed in keratinocytes and had Ca²⁺-independently its activity in the cells. Cyclin G2 was identified as a new target of calcineurin/NFAT pathway in the regulation of the growth of follicular keratinocytes. A cell-permeable NFAT translocation inhibitor (11R-VIVIT) inhibited nuclear import of NFAT1 and consequently reduced the expression of cyclin G2, resulting in induction of hair growth in nude mice. Finally, overexpression of cyclin G2 inhibited 11R-VIVIT-induced keratinocyte growth and hair growth both in vitro and in vivo. [J Physiol Sci. 2008;58 Suppl:S203]