IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis

• ZHU, Weidong

• SHIOJIMA, Ichiro

• ITO, Yuzuru

• LI, Zhi

• IKEDA, Hiroyuki

• YOSHIDA, Masashi

• NAITO, Atsuhiko T.

• NISHI, Jun-ichiro

• UENO, Hiroo

• UMEZAWA, Akihiro

• MINAMINO, Tohru

• NAGAI, Toshio

• KIKUCHI, Akira

• ASASHIMA, Makoto

• KOMURO, Issei

抄録

type:text

[Abstract] Insulin-like growth factor binding proteins (IGFBPs) bind to and modulate the actionsof insulin-like growth factors (IGFs). Although some of the actions of IGFBPs havebeen reported to be independent of IGFs, the precise mechanisms of IGF-independentactions of IGFBPs are largely unknown. Here we report a previously unknownfunction for IGFBP-4 as a cardiogenic growth factor. IGFBP-4 enhancedcardiomyocyte differentiation in vitro, and knockdown of IGFBP-4 attenuatedcardiomyogenesis both in vitro and in vivo. The cardiogenic effect of IGFBP-4 wasindependent of its IGF binding activity but was mediated by the inhibitory effect oncanonical Wnt signaling. IGFBP-4 physically interacted with a Wnt receptor Frizzled 8(Frz8) and a Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6),and inhibited Wnt3A binding to Frz8 and LRP6. Although IGF-independent, thecardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration.Thus, IGFBP-4 is an inhibitor of canonical Wnt signaling required for cardiogenesis,and provides a molecular link between IGF signaling and Wnt signaling.

収録刊行物

• Nature

  Nature 454 345-349, 2008-06-04

  Nature Publishing Group

詳細情報

• CRID: 1050288547193388160
• NII論文ID: 120007069172
• NII書誌ID: AA00752384
• ISSN: 00280836
• ISSN: 14764687
• Web Site: https://opac.ll.chiba-u.jp/da/curator/900047463/
• 本文言語コード: en
• 資料種別: journal article
• データソース種別:
  • IRDB
  • CiNii Articles