Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania.
Department of Hematology, Ion Chiricuta Clinical Cancer Center, Cluj Napoca, Romania.
J Cell Mol Med. 2020 Oct;24(19):11100-11110. doi: 10.1111/jcmm.15526. Epub 2020 Sep 5.
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.
原发性骨髓纤维化（PMF）是一种 Ph 阴性骨髓增殖性肿瘤（MPN），其特征为骨髓纤维化和骨髓外造血明显。骨髓纤维化是由受微环境中多种细胞因子影响的成纤维细胞过度增殖引起的，其中转化生长因子-β（TGF-β）最为重要。与龛位相关的微力学尚未阐明。在这项研究中，我们假设机械应力调节 TGF-β 信号转导，导致骨髓成纤维细胞的进一步激活和随后的增殖和侵袭，从而表明微力学在 PMF 的发生和进展中的重要作用，无论是在骨髓还是骨髓外部位。使用三种 PMF 衍生的成纤维细胞系和 TGFBR1 和 2 敲低 PMF 衍生的成纤维细胞，我们表明机械应力确实通过 TGFBR1 刺激骨髓纤维化患者的成纤维细胞合成胶原，然而，TGFBR2 似乎通过其他途径而非 TGFBR2 被激活。
