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

[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.

https://opac.ll.chiba-u.jp/da/curator/900047463/

https://opac.ll.chiba-u.jp/da/curator/900047463/14764687_454_345.pdf

Nature Publishing Group

学術雑誌論文

AA00752384

Nature

454

345

349

2008-06-04

10.1038/nature07027

author

PubMed 収録論文 （PMC除く）