Erythropoietin-induced metallothionein gene expression: Role in proliferation of K562 cells
Erythropoietin-induced metallothionein gene expression: Role in proliferation of K562 cells
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DOI：
10.1177/153537020322800908
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发表时间：
2003-10-01
影响因子：
3.2
通讯作者：
Agrawal, KC
中科院分区：
文献类型：
--
作者：
Abdel-Mageed, AB;Zhao, FS;Agrawal, KC
最近的证据表明，金属硫蛋白（MT）在红细胞中有明显的表达。然而，造血生长因子对MT蛋白的诱导及其对红系祖细胞克隆扩增或分化的后续功能意义仍然难以捉摸。因此，我们研究了生长因子促红细胞生成素（EPO），粒细胞-单核细胞集落刺激因子（GMCSF），白细胞介素-3（IL-3）对MT基因表达的红系祖细胞K562细胞系。EPO，而不是IL-3或GM-CSF，诱导MT转录在K562细胞中增加3倍。MT诱导与EPO诱导的细胞增殖相关，表明EPO在红系祖细胞中对MT诱导具有特定作用。然而，EPO或丁酸钠诱导的分化，血红蛋白形成的监测被抑制在K562细胞稳定转染含有人MT-IIA基因的表达载体。MT反义硫代磷酸寡核苷酸在这些细胞中部分逆转了这种分化抑制。此外，MT诱导的分化抑制与K562细胞中EPO受体转录物的下调有关。这些数据表明，在红细胞生成所需的生长因子中，EPO是MT的有效诱导剂，并且MT可能在EPO诱导的祖细胞增殖中起重要作用，但在红系特异性分化中不起作用。
Recent evidence has demonstrated an appreciable expression of metallothionein (MT) in erythrocytes. However, the induction of the MT protein by hematopoietic growth factors and its subsequent functional significance on clonal expansion or differentiation of erythroid progenitor cells remain elusive. We therefore examined the effects of growth factors erythropoletin (EPO), granulocyte-monocyte colony-stimulating factor (GMCSF), and interleukin-3 (IL-3) on MT gene expression in erythroid progenitor K562 cell line. EPO, but not IL-3 or GM-CSF, induced a 3-fold increase in MT transcripts in K562 cells. MT induction was associated with EPO-induced cellular proliferation, suggesting a specific role for MT induction by EPO in erythroid progenitor cells. However, EPO- or sodium butyrate-induced differentiation as monitored by hemoglobin formation was inhibited in K562 cells stably transfected with an expression vector containing human MT-IIA gene. This inhibition of differentiation was partially reversed in these cells by an MT antisense phosphorothioate oligonucleotide. Furthermore, the MT-induced inhibition of differentiation was associated with downregulation of EPO receptor transcripts in K562 cells. These data suggest that, among growth factors required for erythropoiesis, EPO is a potent inducer of MT, and that MT may plays a significant role in EPO-induced proliferation, but not in the erythroid-specific differentiation of the progenitor cells.