Thrombopoietin/TGF-β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis

Vittorio Abbonante, Christian A. Di Buduo, Cristian Gruppi, Alessandro Malara, Umberto Gianelli, Giuseppe Celesti, Achille Anselmo, Luigi Andrea Giuseppe Laghi, M. Vercellino, Livia Visai, Alessandra Iurlo, Remigio Moratti, Giovanni Barosi, Vittorio Rosti, A. Balduini

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalStem Cells
DOIs
Publication statusPublished - 2016

Keywords

  • Bone marrow
  • Extracellular matrix
  • Megakaryocytes
  • Thrombopoietin
  • Transforming growth factor-β1

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

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