Thrombopoietin/TGF-1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis
Thrombopoietin/TGF-1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis
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DOI：
10.1002/stem.2285
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发表时间：
2016-04-01
期刊：
影响因子：
5.2
通讯作者：
Balduini, Alessandra
中科院分区：
文献类型：
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作者：
Abbonante, Vittorio;Di Buduo, Christian A.;Balduini, Alessandra
细胞外基质（ECM）成分启动骨髓稳态所需的关键生化和生物力学线索。在我们的研究中，我们证明了主要由III型和IV型胶原和纤连蛋白组成的细胞周围基质包围着骨髓中的人巨核细胞。我们收集的数据支持这一假设，即骨髓巨核细胞具有完整的机制来合成ECM成分，血小板生成素是一个关键的调节剂，这种新的功能诱导转化生长因子-1（TGF-1）的释放和随后的激活下游途径，在体外和体内。这种激活导致巨核细胞的ECM组分合成的剂量依赖性增加，其在与JAK和TGF-1受体特异性抑制剂孵育后恢复。这些数据对于理解巨核细胞在骨髓环境中创建其自身调节小生境的核心作用至关重要。干细胞2016;34：1123-1133
Extracellular matrix (ECM) components initiate crucial biochemical and biomechanical cues that are required for bone marrow homeostasis. In our research, we prove that a peri-cellular matrix composed primarily of type III and type IV collagens, and fibronectin surrounds human megakaryocytes in the bone marrow. The data we collected support the hypothesis that bone marrow megakaryocytes possess a complete mechanism to synthesize the ECM components, and that thrombopoietin is a pivotal regulator of this new function inducing transforming growth factor-1 (TGF-1) release and consequent activation of the downstream pathways, both in vitro and in vivo. This activation results in a dose dependent increase of ECM component synthesis by megakaryocytes, which is reverted upon incubation with JAK and TGF-1 receptor specific inhibitors. These data are pivotal for understanding the central role of megakaryocytes in creating their own regulatory niche within the bone marrow environment. Stem Cells2016;34:1123-1133