Thrombopoietin/TGF-β1 loop regulates megakaryocyte extracellular matrix component synthesis

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, type IV collagens and fibronectin surrounds human megakaryocytes in the bone marrow. The data we collected supports 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-β1 (TGF-β1) 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-β1 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. This article is protected by copyright. All rights reserved