Molecular Medicine Branch, NIDDK, NIH, Bethesda, Maryland, USA.
Curr Opin Hematol. 2010 May;17(3):184-90. doi: 10.1097/MOH.0b013e328337b52f.
Growth differentiation factor 15 (GDF15) was identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. This review addresses the regulation, expression and potential functions of GDF15 in the context of erythroid biology.
GDF15 expression during late erythroid differentiation was discovered as part of an erythroblast transcriptome project. As GDF15 expression is associated with cellular stress or apoptosis, further investigation of the cytokine was focused upon its involvement in ineffective erythropoiesis. Remarkably high serum levels were detected in patients with thalassemia syndromes, congenital dyserythropoiesis and some acquired sideroblastic anemias. High-level GDF15 expression is not a feature of normal erythropoiesis, or erythroid recovery after bone-marrow transplantation. As GDF15 is a transforming growth factor-beta superfamily member, it was investigated as an effector of ineffective erythropoiesis that suppresses hepcidin expression despite iron overloading.
In contrast to the low levels of GDF15 expressed during normal erythropoiesis, ineffective erythropoiesis causes high-level expression of GDF15. In patients with thalassemia and related anemias, GDF15 expression may contribute to iron overloading or other features of the disease phenotype.
生长分化因子 15（GDF15）最初被鉴定为一种抑制铁调素的因子，在无效性红细胞生成患者中高水平表达。本综述讨论了 GDF15 在红细胞生物学中的调节、表达和潜在功能。
作为红系细胞转录组项目的一部分，发现 GDF15 在晚期红系分化过程中表达。由于 GDF15 的表达与细胞应激或细胞凋亡有关，因此对该细胞因子的进一步研究集中在其与无效性红细胞生成的关系上。在地中海贫血综合征、先天性红细胞生成异常和一些获得性铁粒幼细胞性贫血患者中检测到血清中 GDF15 水平显著升高。高水平 GDF15 的表达不是正常红细胞生成或骨髓移植后红细胞生成恢复的特征。由于 GDF15 是转化生长因子-β超家族成员，因此研究其作为无效性红细胞生成的效应因子，尽管存在铁过载，但仍能抑制铁调素的表达。
与正常红细胞生成中表达的低水平 GDF15 相反，无效性红细胞生成导致 GDF15 的高水平表达。在地中海贫血和相关贫血患者中，GDF15 的表达可能导致铁过载或疾病表型的其他特征。
