Keller J R, Jacobsen S E, Dubois C M, Hestdal K, Ruscetti F W
Biological Carcinogenesis and Development Program, PRI/Dyncorp, Inc., Frederick, Maryland.
Int J Cell Cloning. 1992 Jan;10(1):2-11. doi: 10.1002/stem.5530100103.
It is now apparent that the transforming growth factor-beta (TGF-beta) family of proteins has potent hematopoietic regulatory properties ranging from effects on the growth and differentiation of primitive stem cells to the differentiated functions of mature cells. Although most reports have described the inhibitory activities of TGF-beta on hematopoiesis, recent evidence supports the concept that TGF-beta can have both inhibitory and stimulatory actions on these systems. These differences depend on the differentiation state of the target cell and the other cytokines interacting with the cell. Furthermore, TGF-beta has direct bidirectional effects on cell surface expression of many cytokine receptors suggesting that it is part of the mechanism of action of TGF-beta. The major biological effect of TGF-beta on hematopoietic cell growth is the reversible inhibition of entry into the cell cycle. Importantly, the effect of in vivo administration of TGF-beta has mimicked the in vitro effects. Ultimately, well designed clinical trials will determine whether the exciting potential of TGF-beta can be used to treat or prevent myelotoxicity and other bone marrow dysfunctions.
现在很明显，转化生长因子-β（TGF-β）家族的蛋白质具有强大的造血调节特性，范围从对原始干细胞生长和分化的影响到成熟细胞的分化功能。尽管大多数报告描述了TGF-β对造血的抑制活性，但最近的证据支持TGF-β对这些系统可以具有抑制和刺激作用的概念。这些差异取决于靶细胞的分化状态以及与细胞相互作用的其他细胞因子。此外，TGF-β对许多细胞因子受体的细胞表面表达具有直接的双向作用，表明它是TGF-β作用机制的一部分。TGF-β对造血细胞生长的主要生物学效应是对进入细胞周期的可逆抑制。重要的是，体内给予TGF-β的效果模拟了体外效果。最终，精心设计的临床试验将确定TGF-β令人兴奋的潜力是否可用于治疗或预防骨髓毒性和其他骨髓功能障碍。
