Transforming growth factor β-mediated micromechanics modulates disease progression in primary myelofibrosis.
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Bergthorsson, Jon Thor
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CitationTeodorescu P, Pasca S, Jurj A, Gafencu G, Joelsson JP, Selicean S, et al. Transforming growth factor β-mediated micromechanics modulates disease progression in primary myelofibrosis. J Cell Mol Med. 2020 Oct;24(19):11100-11110. doi: 10.1111/jcmm.15526
AbstractPrimary 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. Keywords: TGF-β; fibroblast activation; invasion; micromechanics; myelofibrosis; proliferation.
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Rights© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
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