Cutting the brakes on hematopoietic regeneration by blocking TGFβ to limit chemotherapy-induced myelosuppression.
Cutting the brakes on hematopoietic regeneration by blocking TGFβ to limit chemotherapy-induced myelosuppression.
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DOI：
10.4161/23723556.2014.978703
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发表时间：
2015-07
影响因子：
2.1
通讯作者：
Scandura JM
中科院分区：
文献类型：
--
作者：
Brenet F;Scandura JM
诸如感染、出血或毒性损伤的造血应激源触发造血适应，其牺牲造血干细胞和祖细胞（HSPC）静止以满足对新血细胞产生的迫切需要。一旦造血需求得到充分满足，体内平衡必须恢复。转化生长因子β（Transforming growth factor β，TGFβ）信号传导是应激后HSPC恢复到静止状态的中心介质。造血应激后TGFβ信号传导的阻断延迟了循环HSPC恢复到静止状态，并且这样做促进了造血干细胞（HSC）自我更新并加速了造血重建。这些发现为调节造血适应压力的新疗法打开了大门。在这篇综述中，我们将讨论TGFβ在造血中复杂的环境依赖性活动，以及使用TGFβ通路抑制剂促进骨髓抑制化疗后多系造血重建的潜在益处和局限性。
Hematopoietic stressors such as infection, bleeding, or toxic injury trigger a hematopoietic adaptation that sacrifices hematopoietic stem and progenitor cell (HSPC) quiescence to meet an urgent need for new blood cell production. Once the hematopoietic demands are adequately met, homeostasis must be restored. Transforming growth factor β (TGFβ) signaling is a central mediator mandating the return of HSPCs to quiescence after stress. Blockade of TGFβ signaling after hematopoietic stress delays the return of cycling HSPCs to quiescence and in so doing promotes hematopoietic stem cell (HSC) self-renewal and accelerates hematopoietic reconstitution. These findings open the door to new therapeutics that modulate the hematopoietic adaptation to stress. In this review, we will discuss the complex context-dependent activities of TGFβ in hematopoiesis and the potential benefits and limitations of using TGFβ pathway inhibitors to promote multilineage hematopoietic reconstitution after myelosuppressive chemotherapy.