ArticleThe Journal of biological chemistry2015
Hyaluronan regulates bone morphogenetic protein-7-dependent prevention and reversal of myofibroblast phenotype.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Human Recombinant Hyaluronidase Injections For Upper Limb Muscle Stiffness in Individuals With Cerebral Injury: A Case Series.EBioMedicine · 2016Trial
- Targeting the Calcineurin Homologous Protein 1 (CHP1)-Transmembrane Protein 87A (TMEM87A) mechanosensing complex: a druggable vulnerability in metastatic ovarian cancer.Molecular biomedicine · 2026Article
- Hyaluronan Regulates Vascular Smooth Muscle Cell Osteogenic Differentiation and Vascular Calcification.Biomolecules · 2026Article
- Hyaluronan, a double-edged sword in kidney diseases.Pediatric nephrology (Berlin, Germany) · 2022Review
- Analysis of Human Hyaluronan Synthase Gene Transcriptional Regulation and Downstream Hyaluronan Cell Surface Receptor Mobility in Myofibroblast Differentiation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Myofibroblasts: Function, Formation, and Scope of Molecular Therapies for Skin Fibrosis.Biomolecules · 2021Review
- Design and Evaluation of a Polypeptide that Mimics the Integrin Binding Site for EDA Fibronectin to Block Profibrotic Cell Activity.International journal of molecular sciences · 2021Article
- Enhanced asthma-related fibroblast to myofibroblast transition is the result of profibrotic TGF-β/Smad2/3 pathway intensification and antifibrotic TGF-β/Smad1/5/(8)9 pathway impairment.Scientific reports · 2020Article
- Multifunctional Natural Polymer Nanoparticles as Antifibrotic Gene Carriers for CKD Therapy.Journal of the American Society of Nephrology : JASN · 2020Article
- Hyaluronidase-2 Regulates RhoA Signaling, Myofibroblast Contractility, and Other Key Profibrotic Myofibroblast Functions.The American journal of pathology · 2020Article
- Fibrosis following Acute Skeletal Muscle Injury: Mitigation and Reversal Potential in the Clinic.Journal of sports medicine (Hindawi Publishing Corporation) · 2020Review
- Muscle injury promotes heterotopic ossification by stimulating local bone morphogenetic protein-7 production.Journal of orthopaedic translation · 2019Article
- Resolution of organ fibrosis.The Journal of clinical investigation · 2018Review
- Novel Anti-fibrotic Therapies.Frontiers in pharmacology · 2017Review
- Aberrant transcriptional networks in step-wise neurogenesis of paroxysmal kinesigenic dyskinesia-induced pluripotent stem cells.Oncotarget · 2016Article
- Regulation of synthesis and roles of hyaluronan in peritoneal dialysis.BioMed research international · 2015Review
- Hyaluronan's Role in Fibrosis: A Pathogenic Factor or a Passive Player?BioMed research international · 2015Review
- TMEM2: A New Dimension in Hyaluronan Biology.Proteoglycan researchArticle
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hyaluronan (HA) promotes transforming growth factor (TGF)-β1-driven myofibroblast phenotype. However, HA can also have disease-limiting activity. Bone morphogenetic protein-7 (BMP7) is an antifibrotic cytokine that antagonizes TGF-β1, and isolated studies have demonstrated that HA can both mediate and modulate BMP7 responses. In this study, we investigated whether BMP7 can modulate HA in a manner that leads to prevention/reversal of TGF-β1-driven myofibroblast differentiation in human lung fibroblasts. Results demonstrated that BMP7 prevented and reversed TGF-β1-driven myofibroblast differentiation through a novel mechanism. BMP7 promoted the dissolution and internalization of cell-surface HA into cytoplasmic endosomes. Endosomal HA co-localized with the HA-degrading enzymes, hyaluronidase-1 and hyaluronidase-2 (Hyal2). Moreover, BMP7 showed differential regulation of CD44 standard and variant isoform expression, when compared with TGF-β1. In particular, BMP7 increased membrane expression of CD44v7/8. Inhibiting CD44v7/8 as well as blocking Hyal2 and the Na(+)/H(+) exchanger-1 at the cell-surface prevented BMP7-driven HA internalization and BMP7-mediated prevention/reversal of myofibroblast phenotype. In summary, a novel mechanism of TGF-β1 antagonism by BMP7 is shown and identifies alteration in HA as critical in mediating BMP7 responses. In addition, we identify Hyal2 and CD44v7/8 as new potential targets for manipulation in prevention and reversal of fibrotic pathology.
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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.