@article{7880341660334e6facc4d3f601e64996,
title = "Transforming growth factor β-mediated micromechanics modulates disease progression in primary myelofibrosis",
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.",
keywords = "TGF-β, fibroblast activation, invasion, micromechanics, myelofibrosis, proliferation",
author = "Patric Teodorescu and Sergiu Pasca and Ancuta Jurj and Grigore Gafencu and Joelsson, {Jon Petur} and Sonia Selicean and Cristian Moldovan and Raluca Munteanu and Anca Onaciu and Tigu, {Adrian Bogdan} and Mihail Buse and Zimta, {Alina Andreea} and Rares Stiufiuc and Bobe Petrushev and Minodora Desmirean and Delia Dima and Cristina Vlad and Bergthorsson, {Jon Thor} and Cristian Berce and Stefan Ciurea and Gabriel Ghiaur and Ciprian Tomuleasa",
note = "Funding Information: 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). Funding Information: 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). Publisher Copyright: {\textcopyright} 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.",
year = "2020",
month = oct,
day = "1",
doi = "10.1111/jcmm.15526",
language = "English (US)",
volume = "24",
pages = "11100--11110",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "19",
}