Thrombopoietin/TGF-1 Loop Regulates Megakaryocyte Extracellular Matrix Component Synthesis

被引:49
作者
Abbonante, Vittorio [1 ,3 ]
Di Buduo, Christian A. [1 ,3 ]
Gruppi, Cristian [1 ,3 ]
Malara, Alessandro [1 ,3 ]
Gianelli, Umberto [4 ]
Celesti, Giuseppe [6 ]
Anselmo, Achille [6 ]
Laghi, Luigi [6 ]
Vercellino, Marco [2 ,7 ]
Visai, Livia [2 ,7 ]
Iurlo, Alessandra [5 ]
Moratti, Remigio
Barosi, Giovanni [3 ]
Rosti, Vittorio [3 ]
Balduini, Alessandra [1 ,3 ,8 ]
机构
[1] Univ Pavia, Dept Mol Med, Via Palestro 3, I-27100 Pavia, Italy
[2] Univ Pavia, Ctr Tissue Engn CIT, INSTM UdR Pavia, Via Palestro 3, I-27100 Pavia, Italy
[3] IRCCS San Matteo Fdn, Lab Biotechnol, Pavia, Italy
[4] Univ Milan, Dept Pathophysiol & Transplantat, Div Pathol, Hematopathol Serv, I-20122 Milan, Italy
[5] IRCCS Ca Granda Maggiore Policlin Hosp Fdn, Oncohematol Div, Oncohematol Elderly Unit, Milan, Italy
[6] Humanitas Clin & Res Ctr, Lab Mol Gastroenterol, Milan, Italy
[7] Salvatore Maugeri Fdn FSM, Dept Occupat Med Ergon & Disabil, Lab Nanotechnol, Pavia, Italy
[8] Tufts Univ, Dept Biomed Engn, 4 Colby St, Medford, MA 02155 USA
基金
美国国家卫生研究院;
关键词
Megakaryocytes; Thrombopoietin; Transforming growth factor-1; Extracellular matrix; Bone marrow; BONE-MARROW FIBROSIS; GROWTH-FACTOR-BETA; PROPLATELET FORMATION; TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; FIBRONECTIN SYNTHESIS; EUROPEAN CONSENSUS; COLLAGEN FORMATION; HUMAN-PLASMA; IN-VIVO;
D O I
10.1002/stem.2285
中图分类号
Q813 [细胞工程];
学科分类号
摘要
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-1 (TGF-1) 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-1 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 Cells2016;34:1123-1133
引用
收藏
页码:1123 / 1133
页数:11
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