Open AccessThrombopoietin/TGF‐β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis
Author(s) -
Abbonante Vittorio,
Di Buduo Christian A.,
Gruppi Cristian,
Malara Alessandro,
Gianelli Umberto,
Celesti Giuseppe,
Anselmo Achille,
Laghi Luigi,
Vercellino Marco,
Visai Livia,
Iurlo Alessandra,
Moratti Remigio,
Barosi Giovanni,
Rosti Vittorio,
Balduini Alessandra
Publication year - 2016
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2285
Subject(s) - biology , microbiology and biotechnology , thrombopoietin , megakaryocyte , extracellular matrix , fibronectin , bone marrow , transforming growth factor , immunology , haematopoiesis , stem cell
A bstract 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‐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. S tem C ells 2016;34:1123–1133