Munugalavadla Veerendra, Kapur Reuben
Department of Pediatrics, Herman B Wells Center for Pediatric Research, Cancer Research Building, Indianapolis, IN 46202, USA.
Crit Rev Oncol Hematol. 2005 Apr;54(1):63-75. doi: 10.1016/j.critrevonc.2004.11.005.
Erythropoiesis is regulated by a number of growth factors, among which stem cell factor (SCF) and erythropoietin (Epo) play a non-redundant function. Viable mice with mutations in the SCF gene (encoded by the Steel (Sl) locus), or its receptor gene c-Kit (encoded by the White spotting (W) locus) develop a hypoplastic macrocytic anemia. Mutants of W or Sl that are completely devoid of c-Kit or SCF expression die in utero of anemia between days 14 and 16 of gestation and contain reduced numbers of erythroid progenitors in the fetal liver. Likewise, Epo and Epo receptor (Epo-R)-deficient mice die in utero due to a marked reduction in the number of committed fetal liver derived erythroid progenitors. Thus, committed erythroid progenitors require both c-Kit and Epo-R signal transduction pathways for their survival, proliferation and differentiation. In vitro, Epo alone is capable of generating mature erythroid progenitors; however, a combined treatment of Epo and SCF results in synergistic proliferation and expansion of developing erythroid progenitors. This review summarizes recent advances made towards understanding the signaling mechanisms by which Epo-R and c-Kit regulate growth, survival, and differentiation of erythroid progenitors alone and cooperatively.
红细胞生成受多种生长因子调节，其中干细胞因子（SCF）和促红细胞生成素（Epo）发挥着不可替代的作用。SCF基因（由Steel（Sl）位点编码）或其受体基因c-Kit（由White spotting（W）位点编码）发生突变的存活小鼠会出现发育不全的大细胞性贫血。完全缺乏c-Kit或SCF表达的W或Sl突变体在妊娠第14至16天死于子宫内贫血，且胎肝中的红系祖细胞数量减少。同样，促红细胞生成素（Epo）和促红细胞生成素受体（Epo-R）缺陷型小鼠因胎肝来源的定向红系祖细胞数量显著减少而死于子宫内。因此，定向红系祖细胞的存活、增殖和分化需要c-Kit和Epo-R信号转导通路。在体外，单独的Epo能够产生成熟的红系祖细胞；然而，Epo和SCF联合处理会导致发育中的红系祖细胞协同增殖和扩增。本综述总结了在理解Epo-R和c-Kit单独及协同调节红系祖细胞生长、存活和分化的信号传导机制方面取得的最新进展。
