DISTINCT ROLES OF ERYTHROPOIETIN, INSULIN-LIKE GROWTH-FACTOR-I, AND STEM-CELL FACTOR IN THE DEVELOPMENT OF ERYTHROID PROGENITOR CELLS
DISTINCT ROLES OF ERYTHROPOIETIN, INSULIN-LIKE GROWTH-FACTOR-I, AND STEM-CELL FACTOR IN THE DEVELOPMENT OF ERYTHROID PROGENITOR CELLS
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DOI：
10.1172/jci117327
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发表时间：
1994-07-01
影响因子：
15.9
通讯作者：
WICKREMA, A
中科院分区：
文献类型：
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作者：
MUTA, K;KRANTZ, SB;WICKREMA, A
促红细胞生成素(EP)、胰岛素样生长因子I(IGF-I)和干细胞因子(SCF)均可减少人红系祖细胞的凋亡。为了确定这些生长因子是否具有刺激红细胞生成的额外作用，研究了在无血清液体培养中应用这些生长因子的不同组合对高纯度人红系集落形成细胞(ECFC)的增殖、成熟和存活的影响。EP在红系成熟过程中维持细胞活力并支持血红素的合成，对活细胞数几乎没有增加，对DNA合成的刺激也很小。加入SCF和EP可显著增加DNA合成，其程度大于添加EP时的水平，并与ECFC数量的大幅增加有关。因此，EP本身对细胞增殖的促进作用很小，红系细胞数量的扩大依赖于有EP的干细胞因子的存在。加入IGF-I和EP可促进血红素合成和适度的细胞增殖，但也极大地促进了晚期红细胞的核凝聚和去核。因此，EP本身不足以完成末端核凝聚/去核，而IGF-I的存在是这一完整过程所必需的。当EP在37℃孵育16h时，细胞凋亡率显著减少，而SCF和IGF-I与EP共同作用时，作用不明显，但可使DNA合成增加3.4倍。因此，干细胞因子可能在通过不同于细胞凋亡的过程直接刺激增殖方面发挥额外的作用。我们的观察表明，EP可防止细胞凋亡，并维持红系细胞的存活和发育。IGF-I可促进红系祖细胞的成熟和增殖，但红系祖细胞的增殖主要受干细胞因子与EP共同作用的控制，与细胞凋亡无关。
Erythropoietin (EP), insulin-like growth factor I(IGF-I) and stem cell factor (SCF) each reduce apoptosis of human erythroid progenitor cells. To determine if these growth factors have additional roles in stimulating erythropoiesis, the proliferation, maturation, and survival of highly purified human erythroid colony-forming cells (ECFCs) were studied during the application of different combinations of these growth factors in a serum-free liquid culture. EP maintained cell viability and supported heme synthesis during erythroid maturation, with little increase in viable cell number or stimulation of DNA synthesis. The addition of SCF with EP resulted in a substantial increase in DNA synthesis, which was greater than that seen with the addition of EP and was associated with a large expansion in the number of ECFCs. Thus EP, by itself, produces little increase in cell proliferation, and expansion of the number of erythroid cells depends upon the presence of SCF with EP. The addition of IGF-I with EP led to enhanced heme synthesis and moderate cellular proliferation, but also greatly enhanced nuclear condensation and enucleation in the late erythroblasts. Thus EP, by itself, is not sufficient for complete end-terminal nuclear condensation/enucleation and the presence of IGF-I is necessary for this complete process. While EP greatly reduced apoptosis during 16 h of incubation at 37 degrees C, the addition of SCF and IGF-I with EP had little additional effect, but these additions enhanced DNA synthesis > 3.4-fold. Thus SCF may have an additional role in directly stimulating proliferation through a process that is distinct from apoptosis. Our observations indicate that EP prevents apoptosis and maintains erythroid cell viability and development. IGF-I enhances erythroid maturation and proliferation, but the proliferation of erythroid progenitors is mainly controlled by the addition of SCF with EP, independent of an effect on apoptosis.