MISC

査読有り
2010年1月

Relevant use of Klotho in FGF19 subfamily signaling system in vivo

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
  • Ken-ichi Tomiyama
  • ,
  • Ryota Maeda
  • ,
  • Itaru Urakawa
  • ,
  • Yuji Yamazaki
  • ,
  • Tomohiro Tanaka
  • ,
  • Shinji Ito
  • ,
  • Yoko Nabeshima
  • ,
  • Tsutomu Tomita
  • ,
  • Shinji Odori
  • ,
  • Kiminori Hosoda
  • ,
  • Kazuwa Nakao
  • ,
  • Akihiro Imura
  • ,
  • Yo-ichi Nabeshima

107
4
開始ページ
1666
終了ページ
1671
記述言語
英語
掲載種別
DOI
10.1073/pnas.0913986107
出版者・発行元
NATL ACAD SCIENCES

alpha-Klotho (alpha-Kl) and its homolog, beta-Klotho (beta-Kl) are key regulators of mineral homeostasis and bile acid/cholesterol metabolism, respectively. FGF15/ humanFGF19, FGF21, and FGF23, members of the FGF19 subfamily, are believed to act as circulating metabolic regulators. Analyses of functional interactions between alpha- and beta-Kl and FGF19 factors in wild-type, alpha-kl(-/-), and beta-kl(-/-) mice revealed a comprehensive regulatory scheme of mineral homeostasis involving the mutually regulated positive/negative feedback actions of alpha-Kl, FGF23, and 1,25(OH)(2)D and an analogous regulatory network composed of beta-Kl, FGF15/humanFGF19, and bile acids that regulate bile acid/cholesterol metabolism. Contrary to in vitro data, beta-Kl is not essential for FGF21 signaling in adipose tissues in vivo, because (i) FGF21 signals are transduced in the absence of beta-Kl, (ii) FGF21 could not be precipitated by beta-Kl, and (iii) essential phenotypes in Fgf21(-/-) mice (decreased expressions of Hsl and Atgl in WAT) were not replicated in beta-kl(-/-) mice. These findings suggest the existence of Klotho-independent FGF21 signaling pathway(s) where undefined cofactors are involved. One-to-one functional interactions such as alpha-Klotho/FGF23, beta-Klotho/FGF15 (humanFGF19), and undefined cofactor/FGF21 would result in tissue-specific signal transduction of the FGF19 subfamily.

Web of Science ® 被引用回数 : 110

リンク情報
DOI
https://doi.org/10.1073/pnas.0913986107
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20080590
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000273974600078&DestApp=WOS_CPL
ID情報
  • DOI : 10.1073/pnas.0913986107
  • ISSN : 0027-8424
  • PubMed ID : 20080590
  • Web of Science ID : WOS:000273974600078

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