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

Abstract

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CrossTalkeR: Analysis and Visualisation of Ligand Receptor Networks

“…1E). The strong upregulation of TGFB1-TGFBR1 between MK and MSCs is in line with other publications, showing canonical TGFB1-signaling as most dominant pro-fibrotic element 7 . At the same time, differential expression of co-receptors CD109 and ENG show, how TGFB1-signals are modulated in MF 8,9 .…”

Cardiovascular Disease in Myeloproliferative Neoplasms

“… 4 , 77 MPN has been associated with increased expression and serum levels of TGF-β. 102 , 103 Although older studies suggested that TGF-β may limit atherogenesis, newer evidence suggests a more complex picture and indicates that TGF-β may actually promote atherogenesis. 104 , 105 , 106 One small study noted increased TGF-β expression in platelets of patients with acute coronary syndrome compared with patients with stable coronary artery disease, though lower platelet TGF-β levels were associated with increased mortality.…”

Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies

“…Mutant HSCs can also perturb the well-balanced vascular niche by upregulating several targets involved in neo-angiogenesis (e.g., VEGF and angiopoietin-1) and fibrogenesis (e.g., TGF-β1, CXCL4, PDGF, IL-1β and TNF-α), in order to establish a permissive and nourishing milieu [ 80 , 81 , 82 , 83 ]. In particular, TGF-β1, whose levels are inherently linked to megakaryocytic activity, can induce fibrosis by (i) skewing the activity of MSCs towards fibroblastic and osteoblastic genesis and (ii) increasing the deposition of collagen [ 55 , 84 , 85 ]. Furthermore, evidence from in vitro experiments on PMF models portrayed CXCL4 as a major artificer of BM fibrosis, being able to (i) upregulate pro-fibrotic pathways in megakaryocytes, (ii) induce glioma-associated oncogene homolog 1 (Gli1)+ MSC migration and differentiation into myofibroblasts and (iii) amplify JAK/STAT activation in both megakaryocytes and MSCs [ 86 ].…”

“…The TGF-β superfamily, including activins, growth differentiation factors and bone morphogenetic proteins, plays a major role during signaling in the BM niche, being able to promote oxidative stress, myeloproliferation and fibrosis [ 55 , 85 , 158 ]. Sotatercept and luspatercept are erythroid maturation agents that work as activin receptor ligand traps of IIA and IIB, respectively [ 159 , 160 , 161 , 162 ].…”