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

Fingerprint

Thrombopoietin
Megakaryocytes
Transforming Growth Factors
Extracellular Matrix
Bone Marrow
Collagen Type III
Collagen Type IV
Growth Factor Receptors
Fibronectins
Cues
Homeostasis
Research

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

Thrombopoietin/TGF-β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis. / Abbonante, Vittorio; Di Buduo, Christian A.; Gruppi, Cristian; Malara, Alessandro; Gianelli, Umberto; Celesti, Giuseppe; Anselmo, Achille; Laghi, Luigi Andrea Giuseppe; Vercellino, M.; Visai, Livia; Iurlo, Alessandra; Moratti, Remigio; Barosi, Giovanni; Rosti, Vittorio; Balduini, A.

In: Stem Cells, 2016.

Research output: Contribution to journalArticle

Abbonante, Vittorio ; Di Buduo, Christian A. ; Gruppi, Cristian ; Malara, Alessandro ; Gianelli, Umberto ; Celesti, Giuseppe ; Anselmo, Achille ; Laghi, Luigi Andrea Giuseppe ; Vercellino, M. ; Visai, Livia ; Iurlo, Alessandra ; Moratti, Remigio ; Barosi, Giovanni ; Rosti, Vittorio ; Balduini, A. / Thrombopoietin/TGF-β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis. In: Stem Cells. 2016.
@article{e4b64b4cc7304866bda9ef219229b873,
title = "Thrombopoietin/TGF-β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis",
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.",
keywords = "Bone marrow, Extracellular matrix, Megakaryocytes, Thrombopoietin, Transforming growth factor-β1",
author = "Vittorio Abbonante and {Di Buduo}, {Christian A.} and Cristian Gruppi and Alessandro Malara and Umberto Gianelli and Giuseppe Celesti and Achille Anselmo and Laghi, {Luigi Andrea Giuseppe} and M. Vercellino and Livia Visai and Alessandra Iurlo and Remigio Moratti and Giovanni Barosi and Vittorio Rosti and A. Balduini",
year = "2016",
doi = "10.1002/stem.2285",
language = "English",
journal = "Stem Cells",
issn = "1066-5099",
publisher = "AlphaMed Press",

}

TY - JOUR

T1 - Thrombopoietin/TGF-β1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis

AU - Abbonante, Vittorio

AU - Di Buduo, Christian A.

AU - Gruppi, Cristian

AU - Malara, Alessandro

AU - Gianelli, Umberto

AU - Celesti, Giuseppe

AU - Anselmo, Achille

AU - Laghi, Luigi Andrea Giuseppe

AU - Vercellino, M.

AU - Visai, Livia

AU - Iurlo, Alessandra

AU - Moratti, Remigio

AU - Barosi, Giovanni

AU - Rosti, Vittorio

AU - Balduini, A.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Bone marrow

KW - Extracellular matrix

KW - Megakaryocytes

KW - Thrombopoietin

KW - Transforming growth factor-β1

UR - http://www.scopus.com/inward/record.url?scp=84958212888&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958212888&partnerID=8YFLogxK

U2 - 10.1002/stem.2285

DO - 10.1002/stem.2285

M3 - Article

JO - Stem Cells

JF - Stem Cells

SN - 1066-5099

ER -