Transforming growth factor β-mediated micromechanics modulates disease progression in primary myelofibrosis

Patric Teodorescu, Sergiu Pasca, Ancuta Jurj, Grigore Gafencu, Jon Petur Joelsson, Sonia Selicean, Cristian Moldovan, Raluca Munteanu, Anca Onaciu, Adrian Bogdan Tigu, Mihail Buse, Alina Andreea Zimta, Rares Stiufiuc, Bobe Petrushev, Minodora Desmirean, Delia Dima, Cristina Vlad, Jon Thor Bergthorsson, Cristian Berce, Stefan CiureaGabriel Ghiaur, Ciprian Tomuleasa

Research output: Contribution to journalArticlepeer-review

Abstract

Primary myelofibrosis (PMF) is a Ph-negative myeloproliferative neoplasm (MPN), characterized by advanced bone marrow fibrosis and extramedullary haematopoiesis. The bone marrow fibrosis results from excessive proliferation of fibroblasts that are influenced by several cytokines in the microenvironment, of which transforming growth factor-β (TGF-β) is the most important. Micromechanics related to the niche has not yet been elucidated. In this study, we hypothesized that mechanical stress modulates TGF-β signalling leading to further activation and subsequent proliferation and invasion of bone marrow fibroblasts, thus showing the important role of micromechanics in the development and progression of PMF, both in the bone marrow and in extramedullary sites. Using three PMF-derived fibroblast cell lines and transforming growth factor-β receptor (TGFBR) 1 and 2 knock-down PMF-derived fibroblasts, we showed that mechanical stress does stimulate the collagen synthesis by the fibroblasts in patients with myelofibrosis, through the TGFBR1, which however seems to be activated through alternative pathways, other than TGFBR2.

Original languageEnglish (US)
Pages (from-to)11100-11110
Number of pages11
JournalJournal of Cellular and Molecular Medicine
Volume24
Issue number19
DOIs
StatePublished - Oct 1 2020

Keywords

  • TGF-β
  • fibroblast activation
  • invasion
  • micromechanics
  • myelofibrosis
  • proliferation

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

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