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

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dc.contributor Háskóli Íslands
dc.contributor University of Iceland
dc.contributor.author Teodorescu, Patric
dc.contributor.author Pasca, Sergiu
dc.contributor.author Jurj, Ancuta
dc.contributor.author Gafencu, Grigore
dc.contributor.author Joelsson, Jon‐Petur
dc.contributor.author Selicean, Sonia
dc.contributor.author Moldovan, Cristian
dc.contributor.author Munteanu, Raluca
dc.contributor.author Onaciu, Anca
dc.contributor.author Tigu, Adrian‐Bogdan
dc.contributor.author Buse, Mihail
dc.contributor.author Zimta, Alina‐Andreea
dc.contributor.author Stiufiuc, Rares
dc.contributor.author Petrushev, Bobe
dc.contributor.author Desmirean, Minodora
dc.contributor.author Dima, Delia
dc.contributor.author Vlad, Cristina
dc.contributor.author Bergthorsson, Jon Thor
dc.contributor.author Berce, Cristian
dc.contributor.author Ciurea, Stefan
dc.contributor.author Ghiaur, Gabriel
dc.contributor.author Tomuleasa, Ciprian
dc.date.accessioned 2020-11-09T12:45:13Z
dc.date.available 2020-11-09T12:45:13Z
dc.date.issued 2020-09-05
dc.identifier.citation Teodorescu, P, Pasca, S, Jurj, A, et al. Transforming growth factor‐β‐mediated micromechanics modulates disease progression in primary myelofibrosis.Journal of Cellular and Molecular Medicine. 2020; 24: 11100– 11110. https://doi.org/10.1111/jcmm.15526
dc.identifier.issn 1582-1838
dc.identifier.issn 1582-4934 (eISSN)
dc.identifier.uri https://hdl.handle.net/20.500.11815/2185
dc.description Publisher's version (útgefin grein)
dc.description.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.
dc.description.sponsorship Patric Teodorescu was financed from an internal grant of the School of Doctoral Studies?Iuliu Hatieganu University (PCD 2018-2021). Ciprian Tomuleasa was also supported by two national research grants of the Romanian Government: the first one awarded for Frontiers Research Projects 2018-2022 (grant number PN-III-P4-ID-PCCF-2016-112), awarded to the Babes Bolyai University in collaboration with the Ion Chiricuta Oncology Institute Cluj Napoca; and the second one awarded for Young Research Teams 2020-2022 (grant number PN-III-P1-1.1-TE-2019-0271), awarded to the Iuliu Hatieganu University of Medicine and Pharmacy Cluj Napoca. Ciprian Tomuleasa, Bobe Petrushev and Delia Dima were also financed by an international collaborative grant of the European Economic Space between Romania and Iceland 2020-2022 (grant number 19-COP-0031).
dc.format.extent 11100-11110
dc.language.iso en
dc.publisher Wiley
dc.relation.ispartofseries Journal of Cellular and Molecular Medicine;24(19)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Fibroblast activation
dc.subject Invasion
dc.subject Micromechanics
dc.subject Myelofibrosis
dc.subject Proliferation
dc.subject TGF-β
dc.subject Bandvefur
dc.subject Sameindalíffræði
dc.subject Frumurannsóknir
dc.title Transforming growth factor β‐mediated micromechanics modulates disease progression in primary myelofibrosis
dc.type info:eu-repo/semantics/article
dcterms.license This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
dc.description.version Peer Reviewed
dc.identifier.journal Journal of Cellular and Molecular Medicine
dc.identifier.doi 10.1111/jcmm.15526
dc.relation.url https://onlinelibrary.wiley.com/doi/10.1111/jcmm.15526
dc.contributor.department Lífvísindasetur (HÍ)
dc.contributor.department Biomedical Center (UI)
dc.contributor.school Heilbrigðisvísindasvið (HÍ)
dc.contributor.school School of Health Sciences (UI)

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