日本科学家发现有利于心脏发育的蛋白质

生物谷报道：日本科学家最近发现发现了一种有利于心脏发育的蛋白质。该研究论文发表6月4日发表于《自然》。

科学家通过针对蝌蚪的实验,发现在蝌蚪的心脏发育完成之后,移除蝌蚪体内的IGFBP-4蛋白质，蝌蚪的心脏变得越来越小最后竟然消失了。

研究人员目前尚不清楚IGFBP-4蛋白质是否能在人体胚胎干细胞分化过程中起到作用。但是实验表明IGFBP-4蛋白质在维护心脏健康发育方面能起到非常重要的作用。

IGFBP-4蛋白质是由肝脏产生的。胎儿首先形成的是心脏,然后等生长到中期阶段时,IGFBP-4蛋白质才开始起作用,它对心脏的发育很重要。心脏长成之后,如果IGFBP-4蛋白质被移除,心脏就会慢慢消失。蝌蚪实验证实了这一理论。（生物谷 www.bioon.com）

生物谷推荐原始出处：

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

Weidong Zhu^1,⁸, Ichiro Shiojima^1,⁸, Yuzuru Ito^2,⁸, Zhi Li¹, Hiroyuki Ikeda¹, Masashi Yoshida¹, Atsuhiko T. Naito¹, Jun-ichiro Nishi¹, Hiroo Ueno³, Akihiro Umezawa⁴, Tohru Minamino¹, Toshio Nagai¹, Akira Kikuchi⁵, Makoto Asashima^2,^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: komuro-tky@umin.ac.jp).

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 unknown^1,². 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.