Transforming growth factor β‐mediated micromechanics modulates disease progression in primary myelofibrosis
Year: 2020
Type: article
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.
DOI: 10.1111/jcmm.15526
Authors: 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 Ciurea, Gabriel Ghiaur, Ciprian Tomuleasa
Institutions: Iuliu Hațieganu University of Medicine and Pharmacy, Institute of Oncology Prof. Dr. Ion Chiricuta, John Radcliffe Hospital, University of Oxford, MRC Weatherall Institute of Molecular Medicine, University of Iceland, National University Hospital of Iceland, University of Bern, The University of Texas MD Anderson Cancer Center, Johns Hopkins University, Johns Hopkins Medicine, Sidney Kimmel Comprehensive Cancer Center
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,080
OpenAlex ID: W3083070931