Involvement of TGF 1 in autocrine regulation of proplatelet formation in healthy subjects and patients with primary myelofibrosis
Open accessAbstract
Megakaryocytes release platelets into the bloodstream by elongating proplatelets. In this study, we showed that human megakaryocytes constitutively release Transforming Growth Factor β1 and express its receptors. Importantly, Transforming Growth Factor β1 downstream signaling, through SMAD2/3 phosphorylation, was shown to be active in megakaryocytes extending proplatelets, indicating a type of autocrine stimulation on megakaryocyte development. Furthermore, inactivation of Transforming Growth Factor β1 signaling, by the receptor inhibitors SB431542 and Stemolecule ALK5 inhibitor, determined a significant decrease in proplatelet formation. Recent studies indicated a crucial role of Transforming Growth Factor β1 in the pathogenesis of primary myelofibrosis. We demonstrated that primary myelofibrosis-derived megakaryocytes expressed increased levels of bioactive Transforming Growth Factor β1; however, higher levels of released Transforming Growth Factor β1 did not lead to enhanced activation of downstream pathways. Overall, these data propose Transforming Growth Factor β1 as a new element in the autocrine regulation of proplatelet formation in vitro. Despite the increase in Transforming Growth Factor β1 this mechanism seems to be preserved in primary myelofibrosis.
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TGFB1 was downregulated upon IFNa treatment.
“We also observed a downregulation of TGFB1 ( Supplementary Fig. 4b ), that encodes the pro-fibrotic cytokine TGFb established as one of the main inducers of myelofibrosis in patients with fibrotic-phase of MPN 50,51 .”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [50]
The citation is attached to the background claim about TGFβ and myelofibrosis, not to the citing authors’ observation of TGFB1 downregulation after IFNα treatment. The source describes TGFβ1 as having a crucial role in primary myelofibrosis pathogenesis, but its discussion of TGFβ1 promoting bone-marrow fibrosis is framed as a hypothesis, not an established finding that it is one of the main inducers. (LLM, conf=0.84)
Experimental — accuracy not yet measuredTGFB1 encodes the pro-fibrotic cytokine TGFb, established as one of the main inducers of myelofibrosis in patients with fibrotic-phase MPN.
“We also observed a downregulation of TGFB1 ( Supplementary Fig. 4b ), that encodes the pro-fibrotic cytokine TGFb established as one of the main inducers of myelofibrosis in patients with fibrotic-phase of MPN 50,51 .”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [50]
The Introduction states that TGFβ1 is a major contributor to bone-marrow fibrosis in disorders including myelofibrosis, and identifies primary myelofibrosis as a myeloproliferative neoplasm. It does not specifically address patients in the fibrotic phase of MPN or state that the TGFB1 gene encodes TGFβ. (LLM, conf=0.83)
Experimental — accuracy not yet measuredMPN megakaryocytes exhibit higher expression of TGFB1.
“We and others have shown that MPN megakaryocytes indeed exhibit higher expression of TGFB1 20,50,51 , and thus downregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [50]
Figure 2 and the results (p. 516) show that megakaryocytes from patients with primary myelofibrosis released more total and bioactive TGFβ1 than healthy controls. The paper does not establish higher TGFB1 gene expression or show that the finding extends to MPN megakaryocytes generally. The IFNa proposal follows the cited clause and is not treated as attributed to this source. (LLM, conf=0.84)
Experimental — accuracy not yet measuredDownregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.
“We and others have shown that MPN megakaryocytes indeed exhibit higher expression of TGFB1 20,50,51 , and thus downregulation of TGFB1 by IFNa may be a key mechanism of improvement in fibrosis frequently observed in patients treated with IFNa.”
From Type 1 interferon perturbates clonal competition by reshaping human blood development (2026) · cites this paper as [50]
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- Authors
- Badalucco, S., Di Buduo, C. A., Campanelli, R., Pallotta, I., Catarsi, P., Rosti, V., Kaplan, D. L., Barosi, G., Massa, M., & Balduini, A.
- Affiliations
- University of Pavia (IT)
- Tufts University (US)
- Venue
- Haematologica
- Published
- 2013-02-12
- Volume
- 98
- Issue
- 4
- Pages
- 514-517
- ISSN
- 0390-6078 (ISSN-L)
- 1592-8721
- PMC
- PMC3659980
- OpenAlex
- W2153623293
- Cited by
- 37
- References
- 21
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 5 · 2017: 3 · 2016: 3 · 2015: 5 · 2014: 4 · 2013: 1
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Haematologica (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Fondazione Cariplo
- Associazione Italiana per la Ricerca sul Cancro (5X 1000)
- Regione Lombardia
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (R01EB016041)
- Topics
- Health Sciences › Medicine › Hematology › Platelet Disorders and Treatments
- Health Sciences › Medicine › Genetics › Myeloproliferative Neoplasms: Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- TGF-β1, proplatelet formation, megakaryocytes, autocrine regulation, primary myelofibrosis, Smad2/3 signaling, TGF-beta receptor, ALK5 inhibition, SB431542, platelet release, megakaryopoiesis
- MeSH terms
- Receptor, Transforming Growth Factor-beta Type I, Receptor, Transforming Growth Factor-beta Type II, Benzamides, Blood Platelets, Cells, Cultured, Dioxoles, Humans, Megakaryocytes, Phosphorylation, Blotting, Western, Signal Transduction, Gene Expression, Protein Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Autocrine Communication, Reverse Transcriptase Polymerase Chain Reaction, Smad2 Protein, Smad3 Protein, Transforming Growth Factor beta1, Primary Myelofibrosis
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