このエントリーをはてなブックマークに追加
ID 49567
フルテキストURL
著者
Fujimura, Atsushi Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci
Michiue, Hiroyuki Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci 科研費研究者番号
Nishiki, Tei-ichi Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci 科研費研究者番号
Ohmori, Iori Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci 科研費研究者番号
Wei, Fanyan Kumamoto Univ, Dept Mol Physiol, Fac Life Sci
Matsui, Hideki Okayama Univ, Dept Physiol, Grad Sch Med Dent & Pharmaceut Sci 科研費研究者番号
Tomizawa, Kazuhito Kumamoto Univ, Dept Mol Physiol, Fac Life Sci
抄録
Hair growth is a highly regulated cyclical process. Immunosuppressive immunophilin ligands such as cyclosporin A (CsA) and FK506 are known as potent hair growth modulatory agents in rodents and humans that induce active hair growth and inhibit hair follicle regression. The immunosuppressive effectiveness of these drugs has been generally attributed to inhibition of T cell activation through well-characterized pathways. Specifically, CsA and FK506 bind to intracellular proteins, principally cyclophilin A and FKBP12, respectively, and thereby inhibit the phosphatase calcineurin (Cn). The calcineurin (Cn)/NFAT pathway has an important, but poorly understood, role in the regulation of hair follicle development. Here we show that a novel-splicing variant of calcineurin A beta CnA beta-FK, which is encoded by an intron-retaining mRNA and is deficient in the autoinhibitory domain, is predominantly expressed in mature follicular keratinocytes but not in the proliferating keratinocytes of rodents. CnA beta-FK was weakly sensitive to Ca(2+) and dephosphorylated NFATc2 under low Ca(2+) levels in keratinocytes. Inhibition of Cn/NFAT induced hair growth in nude mice. Cyclin G2 was identified as a novel target of the Cn/NFATc2 pathway and its expression in follicular keratinocytes was reduced by inhibition of Cn/NFAT. Overexpression of cyclin G2 arrested the cell cycle in follicular keratinocytes in vitro and the Cn inhibitor, cyclosporin A, inhibited nuclear localization of NFATc2, resulting in decreased cyclin G2 expression in follicular keratinocytes of rats in vivo. We therefore suggest that the calcineurin/NFAT pathway has a unique regulatory role in hair follicle development.
発行日
2011-05-14
出版物タイトル
PLoS ONE
6巻
3号
出版者
Public Library Science
ISSN
1932-6203
資料タイプ
学術雑誌論文
オフィシャル URL
http://dx.doi.org/10.1371/journal.pone.0017685
関連URL
http://ousar.lib.okayama-u.ac.jp/metadata/49130
言語
English
論文のバージョン
publisher
査読
有り
DOI
Web of Sience KeyUT