ArticleAging2021
IGFBP-6/sonic hedgehog/TLR4 signalling axis drives bone marrow fibrotic transformation in primary myelofibrosis.
Article in Aging, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 43 citations in OpenAlex.
- Renal IGFBP6 Interacts With THBS1 to Drive Renal Cellular Senescence and Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-Cell Profiling Reveals RAB13Aging cell · 2026Article
- Review
- Pathologic Signaling and Disease Implications of Insulin-like Growth Factor Binding Proteins in Cancer, Cardiovascular Disease, and Fibrosis.International journal of molecular sciences · 2025Review
- Redox Biology and Insulin-like Growth Factor-Binding Protein-6: A Potential Relationship.Biology · 2025Review
- Cancer associated fibroblasts in tumors: focusing on solid tumors and hematological malignancies.Frontiers in oncology · 2025Review
- Cardiac fibroblast-derived IGFBP6 orchestrates cardiac remodeling by coupling the EGR1-MFAP4 axis.International journal of biological sciences · 2025Article
- Hedgehog Signaling Pathway in Fibrosis and Targeted Therapies.Biomolecules · 2024Review
- Mechanobiology and Primary Cilium in the Pathophysiology of Bone Marrow Myeloproliferative Diseases.International journal of molecular sciences · 2024Review
- (+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease.Journal of translational medicine · 2024Article
- Review
- Engagement of Mesenchymal Stromal Cells in the Remodeling of the Bone Marrow Microenvironment in Hematological Cancers.Biomolecules · 2023Review
- Fibrosis and bone marrow: understanding causation and pathobiology.Journal of translational medicine · 2023Review
- Signaling Pathways of the Insulin-like Growth Factor Binding Proteins.Endocrine reviews · 2023Article
- The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.Metabolites · 2023Review
- IGFBP-6 Network in Chronic Inflammatory Airway Diseases and Lung Tumor Progression.International journal of molecular sciences · 2023Review
- IGFBP-6 Alters Mesenchymal Stromal Cell Phenotype Driving Dasatinib Resistance in Chronic Myeloid Leukemia.Life (Basel, Switzerland) · 2023Article
- Cancer-associated fibroblasts in hematologic malignancies: elucidating roles and spotlighting therapeutic targets.Frontiers in oncology · 2023Review
- Myofibroblast Ccn3 is regulated by Yap and Wwtr1 and contributes to adverse cardiac outcomes.Frontiers in cardiovascular medicine · 2023Article
- Mesenchymal stromal cells in tumor microenvironment remodeling of BCR-ABL negative myeloproliferative diseases.Frontiers in oncology · 2023Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primary myelofibrosis is a Ph-negative chronic myeloproliferative neoplasm characterized by bone marrow fibrosis and associated with the involvement of several pathways, in addition to bone marrow microenvironment alterations, mostly driven by the activation of the cytokine receptor/JAK2 pathway. Identification of driver mutations has led to the development of targeted therapy for myelofibrosis, contributing to reducing inflammation, although this currently does not translate into bone marrow fibrosis remission. Therefore, understanding the clear molecular cut underlying this pathology is now necessary to improve the clinical outcome of patients. The present study aims to investigate the involvement of IGFBP-6/sonic hedgehog /Toll-like receptor 4 axis in the microenvironment alterations of primary myelofibrosis. We observed a significant increase in IGFBP-6 expression levels in primary myelofibrosis patients, coupled with a reduction to near-normal levels in primary myelofibrosis patients with JAK2V617F mutation. We also found that both IGFBP-6 and purmorphamine, a SHH activator, were able to induce mesenchymal stromal cells differentiation with an up-regulation of cancer-associated fibroblasts markers. Furthermore, TLR4 signaling was also activated after IGFBP-6 and purmorphamine exposure and reverted by cyclopamine exposure, an inhibitor of the SHH pathway, confirming that SHH is involved in TLR4 activation and microenvironment alterations. In conclusion, our results suggest that the IGFBP-6/SHH/TLR4 axis is implicated in alterations of the primary myelofibrosis microenvironment and that IGFBP-6 may play a central role in activating SHH pathway during the fibrotic process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.