生物谷報道:日本科學(xué)家最近發(fā)現(xiàn)發(fā)現(xiàn)了一種有利于心臟發(fā)育的蛋白質(zhì)。該研究論文發(fā)表6月4日發(fā)表于《自然》,。
科學(xué)家通過針對蝌蚪的實(shí)驗(yàn),發(fā)現(xiàn)在蝌蚪的心臟發(fā)育完成之后,移除蝌蚪體內(nèi)的IGFBP-4蛋白質(zhì),,蝌蚪的心臟變得越來越小最后竟然消失了,。
研究人員目前尚不清楚IGFBP-4蛋白質(zhì)是否能在人體胚胎干細(xì)胞分化過程中起到作用。但是實(shí)驗(yàn)表明IGFBP-4蛋白質(zhì)在維護(hù)心臟健康發(fā)育方面能起到非常重要的作用,。
IGFBP-4蛋白質(zhì)是由肝臟產(chǎn)生的,。胎兒首先形成的是心臟,然后等生長到中期階段時,IGFBP-4蛋白質(zhì)才開始起作用,它對心臟的發(fā)育很重要。心臟長成之后,如果IGFBP-4蛋白質(zhì)被移除,心臟就會慢慢消失,。蝌蚪實(shí)驗(yàn)證實(shí)了這一理論,。(生物谷www.bioon.com)
生物谷推薦原始出處:
IGFBP-4 is an inhibitor of canonical Wnt signalling required for cardiogenesis
Weidong Zhu1,8, Ichiro Shiojima1,8, Yuzuru Ito2,8, Zhi Li1, Hiroyuki Ikeda1, Masashi Yoshida1, Atsuhiko T. Naito1, Jun-ichiro Nishi1, Hiroo Ueno3, Akihiro Umezawa4, Tohru Minamino1, Toshio Nagai1, Akira Kikuchi5, Makoto Asashima2,6,7 & Issei Komuro1
Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
ICORP Organ Regeneration Project, Japan Science and Technology Agency (JST), Tokyo 153-8902, Japan
Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California 94305, USA
Department of Reproductive Biology, National Institute for Child Health and Development, Tokyo 157-8535, Japan
Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan
Department of Life Sciences (Biology), Graduate School of Arts and Science, The University of Tokyo, Tokyo 153-8902, Japan
National Institute of Advanced Industrial Sciences and Technology (AIST), Ibaraki 305-8562, Japan
These authors contributed equally to this work.
Correspondence to: Issei Komuro1 Correspondence and requests for materials should be addressed to I.K. (Email: [email protected]).
Insulin-like growth-factor-binding proteins (IGFBPs) bind to and modulate the actions of insulin-like growth factors (IGFs)1. Although some of the actions of IGFBPs have been reported to be independent of IGFs, the precise mechanisms of IGF-independent actions of IGFBPs are largely unknown1, 2. Here we report a previously unknown function for IGFBP-4 as a cardiogenic growth factor. IGFBP-4 enhanced cardiomyocyte differentiation in vitro, and knockdown of Igfbp4 attenuated cardiomyogenesis both in vitro and in vivo. The cardiogenic effect of IGFBP-4 was independent of its IGF-binding activity but was mediated by the inhibitory effect on canonical Wnt signalling. 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 the binding of Wnt3A to Frz8 and LRP6. Although IGF-independent, the cardiogenic effect of IGFBP-4 was attenuated by IGFs through IGFBP-4 sequestration. IGFBP-4 is therefore an inhibitor of the canonical Wnt signalling required for cardiogenesis and provides a molecular link between IGF signalling and Wnt signalling.