FLRG, member of the follistatin family, a new player in hematopoiesis
FLRG, member of the follistatin family, a new player in hematopoiesis
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DOI：
10.1016/j.mce.2004.07.009
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发表时间：
2004-10-15
影响因子：
4.1
通讯作者：
Rimokh, R
中科院分区：
文献类型：
--
作者：
Maguer-Satta, W;Rimokh, R
几年前，我们从B细胞白血病中克隆并鉴定了一种新的分泌蛋白，基于其与卵泡抑素的高度结构同源性，将其定义为卵泡抑素家族的成员，并因此命名为卵泡抑素相关基因（FLRG）。然而，卵泡抑素和FLRG揭示了在各种组织中的非重叠表达模式，从而表明这些蛋白质在整个生物体中存在非冗余的功能作用。长期以来，卵泡抑素是各种细胞系统中激活素和骨形态发生蛋白（BMP）功能的生物调节剂：特别是，它抑制激活素对造血的作用。因此，我们研究了FLRG在人造血过程中的表达和作用，特别关注这种可溶性糖蛋白在红细胞生成调节中的作用。为此，我们首次比较了激活素A、BMP 2和BMP 4在原代人类细胞中红细胞生成过程中的作用。我们的研究结果表明，BMP 2作用于早期红系细胞，而激活素A作用于更分化的群体。我们报告了在没有EPO的情况下，激活素A和BMP 2诱导细胞向红细胞生成的定型。这种诱导涉及两个关键事件：EPO-R的增加和GATA 2表达的减少。我们的研究结果表明，尽管它们的高结构同源性，卵泡抑素和FLRG不调节相同的信号转导靶点，因此突出了这两种蛋白质在人类造血系统中的不同功能和机制。因此，我们提出了一个工作模型的调节激活素或BMP诱导的人类红细胞生成卵泡抑素/FLRG。(C)2004爱思唯尔爱尔兰有限公司保留所有权利。
Several years ago, we cloned and characterized from a B cell leukemia a new secreted protein which, on the basis of its high degree of structural homology with follistatin, was defined as a member of the follistatin family and accordingly named follistatin-related gene (FLRG). However, follistatin and FLRG revealed non-overlapping patterns of expression in various tissues thereby indicating the existence of non-redundant functional roles for these proteins throughout the organism. As known for a long time, follistatin is a biological regulator of activin and bone morphogenetic protein (BMP) function in various cellular systems: in particular, it inhibits the effects of activin on hematopoiesis. We therefore investigated the expression and effects of FLRG during human hematopoiesis with particular focus on the effect of this soluble glycoprotein in the regulation of erythropoiesis. For this purpose, we have for the first time, compared the role of Activin A, BMP2 and BMP4 during erythropoiesis, in primary human cells. Our results indicate that, BMP2 acts on early erythroid cells while Activin A acts on a more differentiated population. We report the induction by Activin A and BMP2 of cell commitment towards erythropoiesis in the absence of EPO. This induction involves two key events: increase of EPO-R and the decrease of GATA2 expression. Our results indicate that despite their high structural homology, follistatin and FLRG do not regulate the same signaling targets, therefore highlighting distinct functions and mechanisms for these two proteins in the human hematopoietic system. We thus propose a working model for the regulation of activin or BMP-induced human erythropoiesis by follistatin/FLRG. (C) 2004 Elsevier Ireland Ltd. All rights reserved.