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

• Published in: Journal of Cellular and Molecular Medicine
• Main Authors: Teodorescu, Patric, Pasca, Sergiu, Jurj, Ancuta, Gafencu, Grigore, Joelsson, Jon-Petur, Selicean, Sonia, Moldovan, Cristian, Munteanu, Raluca, Onaciu, Anca, Tigu, Adrian-Bogdan, Buse, Mihail, Zimta, Alina-Andreea, Stiufiuc, Rares, Petrushev, Bobe, Desmirean, Minodora, Dima, Delia, Vlad, Cristina, Bergthorsson, Jon Thor, Berce, Cristian, Ciurea, Stefan, Ghiaur, Gabriel, Tomuleasa, Ciprian
• Other Authors: 1Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania. 2Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj Napoca, Romania. 3Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania. 4Molecular Haematology Unit - Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK. 5Stem Cell Research Unit, Biomedical Center, School of Health Sciences, University of Iceland, Reykjavík, Iceland. 6Department of Laboratory Hematology, Landspitali University Hospital, Reykjavík, Iceland. 7Graduate School for Cellular and Biomedical Sciences, Universität Bern, Bern, Switzerland. 8Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania. 9Department of Pathology, Constantin Papilian Military Hospital, Cluj Napoca, Romania. 10Department of Hematology, Ion Chiricuta Clinical Research Center, Cluj Napoca, Romania. 11Department of Cardiology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania. 12Department of Cardiology, Rehabilitation Hospital, Cluj Napoca, Romania. 13Department of Laboratory Hematology, Landspitali, University Hospital, Reykjavík, Iceland. 14Animal Facility, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania. 15Department of Cellular Therapies and Stem Cell Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX, USA. 16Department of Leukemia, Sidney Kimmel Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2020
• Subjects: TGF-β; fibroblast activation; invasion; micromechanics; myelofibrosis; proliferation; Primary Myelofibrosis; Iceland
• Online Access: http://hdl.handle.net/2336/621564; https://doi.org/10.1111/jcmm.15526

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download 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. School of Doctoral Studies-Iuliu Hatieganu University Romanian Government Ion Chiricuta Oncology Institute Cluj Napoca international collaborative grant of the European Economic Space between Romania and Iceland 2020-2022 19