Involvement of TGFβ1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis

Stefania Badalucco, Christian Andrea Di Buduo, Rita Campanelli, Isabella Pallotta, Paolo Catarsi, Vittorio Rosti, David L. Kaplan, Giovanni Barosi, Margherita Massa, Alessandra Balduini

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Abstract

Megakaryocytes release platelets into the bloodstream by elongating proplatelets. In this study, we showed that human megakaryocytes constitutively release Transforming Growth Factor β1 and express its receptors. Importantly, Transforming Growth Factor β1 downstream signaling, through SMAD2/3 phosphorylation, was shown to be active in megakaryocytes extending proplatelets, indicating a type of autocrine stimulation on megakaryocyte development. Furthermore, inactivation of Transforming Growth Factor β1 signaling, by the receptor inhibitors SB431542 and Stemolecule ALK5 inhibitor, determined a significant decrease in proplatelet formation. Recent studies indicated a crucial role of Transforming Growth Factor β1 in the pathogenesis of primary myelofibrosis. We demonstrated that primary myelofibrosis-derived megakaryocytes expressed increased levels of bioactive Transforming Growth Factor β1; however, higher levels of released Transforming Growth Factor β1 did not lead to enhanced activation of downstream pathways. Overall, these data propose Transforming Growth Factor β1 as a new element in the autocrine regulation of proplatelet formation in vitro. Despite the increase in Transforming Growth Factor β1 this mechanism seems to be preserved in primary myelofibrosis.

Original languageEnglish
Pages (from-to)514-517
Number of pages4
JournalHaematologica
Volume98
Issue number4
DOIs
Publication statusPublished - Apr 2013

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Primary Myelofibrosis
Transforming Growth Factors
Healthy Volunteers
Megakaryocytes
Blood Platelets
Phosphorylation

ASJC Scopus subject areas

  • Hematology

Cite this

Involvement of TGFβ1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis. / Badalucco, Stefania; Di Buduo, Christian Andrea; Campanelli, Rita; Pallotta, Isabella; Catarsi, Paolo; Rosti, Vittorio; Kaplan, David L.; Barosi, Giovanni; Massa, Margherita; Balduini, Alessandra.

In: Haematologica, Vol. 98, No. 4, 04.2013, p. 514-517.

Research output: Contribution to journalArticle

Badalucco, Stefania ; Di Buduo, Christian Andrea ; Campanelli, Rita ; Pallotta, Isabella ; Catarsi, Paolo ; Rosti, Vittorio ; Kaplan, David L. ; Barosi, Giovanni ; Massa, Margherita ; Balduini, Alessandra. / Involvement of TGFβ1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis. In: Haematologica. 2013 ; Vol. 98, No. 4. pp. 514-517.
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