2 FORMS OF TRANSFORMING GROWTH-FACTOR-BETA DISTINGUISHED BY MULTIPOTENTIAL HEMATOPOIETIC PROGENITOR CELLS
2 FORMS OF TRANSFORMING GROWTH-FACTOR-BETA DISTINGUISHED BY MULTIPOTENTIAL HEMATOPOIETIC PROGENITOR CELLS
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DOI：
10.1038/329539a0
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发表时间：
1987-10-08
期刊：
影响因子：
64.8
通讯作者：
MASSAGUE, J
中科院分区：
文献类型：
--
作者：
OHTA, M;GREENBERGER, JS;MASSAGUE, J
β型转化生长因子（TGF-βs）是一种多肽，其在控制许多细胞类型的增殖和分化方面起重要作用1，2。已经鉴定了两种不同的同源二聚体TGF-β多肽，TGF-β1和TGF-β2，其显示出超过70%的氨基酸序列相似性3，4。尽管它们的结构存在差异，但TGF-β1和TGF-β2在抑制上皮细胞增殖和成脂分化方面同样有效3。最近的免疫组织化学定位高水平的TGF-β在骨髓和造血祖细胞的胎儿肝脏5提出了可能性，TGF-βs可能参与调节造血。在这里，我们表明，TGF-β1，而不是TGF-β2，是造血祖细胞增殖的有效抑制剂。TGF-β1抑制小鼠因子依赖性造血祖细胞对白细胞介素-3（IL-3）或粒细胞-巨噬细胞集落刺激因子（GM-CSF）的集落形成，以及骨髓祖细胞对CSF-1（M-CSF）的集落形成。所检查的祖细胞系对TGF-β1的敏感性是TGF-β2的100倍，并且显示I型TGF-β受体对TGF-β1的亲和力是TGF-β2的20倍。这些结果将TGF-β1鉴定为一种新的造血调节因子，其通过I型TGF-β受体调节祖细胞对造血生长因子的反应而增殖。
Type-β transforming growth factors (TGF-βs) are polypeptides that act hormonally to control proliferation and differentiation of many cell types1,2. Two distinct homodimeric TGF-β polypeptides, TGF-β1 and TGF-β2 have been identified which show ˜70% amino-acid sequence similarity3,4. Despite their structural differences, TGF-β1 and TGF-β2 are equally potent at inhibiting epithelial cell proliferation and adipogenic differentiation3. The recent immunohistochemical localization of high levels of TGF-β in the bone marrow and haematopoietic progenitors of the fetal liver5has raised the possibility that TGF-βs might be involved in the regulation of haematopoiesis. Here we show that TGF-β1, but not TGF-β2, is a potent inhibitor of haematopoietic progenitor cell proliferation. TGF-β1 inhibited colony formation by murine factor-dependent haematopoietic progenitor cells in response to interleukin-3 (IL-3) or granulocyte-macrophage colony stimulating factor (GM-CSF), as well as colony formation by marrow progenitor cells responding to CSF-1 (M-CSF). The progenitor cell lines examined were ˜100-fold more sensitive to TGF-β1 than TGF-β2, and displayed type-I TGF-β receptors with affinity ˜20-fold higher for TGF-β1 than TGF-β2. These results identify TGF-β1 as a novel regulator of haematopoiesis that acts through type-I TGF-β receptors to modulate proliferation of progenitor cells in response to haematopoietic growth factors.