Thrombopoietin/TGF‐β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis. (29th January 2016)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Stem cells. Volume 34:Number 4(2016:Apr.)
• Page Start: 1123
• Page End: 1133
• Publication Date: 2016-01-29
• Subjects: Megakaryocytes -- Thrombopoietin -- Transforming growth factor‐β1 -- Extracellular matrix -- Bone marrow; Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2285
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract : 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. Stem Cells 2016;34:1123–1133