[發育] 日本科學家發現有利于心臟發育的蛋白質
日本科學家最近發現發現了一種有利于心臟發育的蛋白質。該研究論文發表
6月4日發表于《自然》。
科學家通過針對蝌蚪的實驗,發現在蝌蚪的心臟發育完成之後,移除蝌蚪體內
的IGFBP-4蛋白質，蝌蚪的心臟變得越來越小最後竟然消失了。
研究人員目前尚不清楚IGFBP-4蛋白質是否能在人體胚胎幹細胞分化過程中起
到作用。但是實驗表明IGFBP-4蛋白質在維護心臟健康發育方面能起到非常重
要的作用。
IGFBP-4蛋白質是由肝臟產生的。胎兒首先形成的是心臟,然後等生長到中期
階段時,IGFBP-4蛋白質才開始起作用,它對心臟的發育很重要。心臟長成之後
,如果IGFBP-4蛋白質被移除,心臟就會慢慢消失。蝌蚪實驗證實了這一理論。
IGFBP-4 is an inhibitor of canonical Wnt signalling required for
cardiogenesis
nsulin-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.
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