ArticleRespiratory research2015
Megakaryoblastic leukemia-1 is required for the development of bleomycin-induced pulmonary fibrosis.
Article in Respiratory research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Development and characterization of an inducible Tensin1 deficient transgenic murine model.Scientific reports · 2026Article
- The fibronectin-targeting PEG-FUD imaging probe shows enhanced uptake during fibrogenesis in experimental lung fibrosis.Respiratory research · 2025Article
- [Science advances · 2024Article
- Inhibition of MRTF activation as a clinically achievable anti-fibrotic mechanism for pirfenidone.The European respiratory journal · 2023Article
- Myofibroblast-specific inhibition of the Rho kinase-MRTF-SRF pathway using nanotechnology for the prevention of pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- [European journal of nuclear medicine and molecular imaging · 2022Article
- Selective Inhibition of Bromodomain-Containing Protein 4 Reduces Myofibroblast Transdifferentiation and Pulmonary Fibrosis.Frontiers in molecular medicine · 2022Article
- Expression of serum response factor in the lung mesenchyme is essential for development of pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Article
- MKL1-induced lncRNA SNHG18 drives the growth and metastasis of non-small cell lung cancer via the miR-211-5p/BRD4 axis.Cell death & disease · 2021Article
- Resident Fibroblast MKL1 Is Sufficient to Drive Pro-fibrogenic Response in Mice.Frontiers in cell and developmental biology · 2021Article
- Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies.Trends in pharmacological sciences · 2020Review
- Molecular Mechanisms of Pulmonary Fibrogenesis and Its Progression to Lung Cancer: A Review.International journal of molecular sciences · 2019Review
- Mechanisms for the Resolution of Organ Fibrosis.Physiology (Bethesda, Md.) · 2019Review
- Lung carcinogenesis and fibrosis taken together: just coincidence?Current opinion in pulmonary medicine · 2017Review
- Releasing Tensin.American journal of respiratory cell and molecular biology · 2017Article
- Tensin 1 Is Essential for Myofibroblast Differentiation and Extracellular Matrix Formation.American journal of respiratory cell and molecular biology · 2017Article
- "Scar-cinoma": viewing the fibrotic lung mesenchymal cell in the context of cancer biology.The European respiratory journal · 2016Article
- Transcriptional control of cardiac fibroblast plasticity.Journal of molecular and cellular cardiology · 2016Review
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Authors and funding
7 authors.
Funding
Abstract
backgroundFibrosing disorders of the lung, such as idiopathic pulmonary fibrosis, are characterized by progressive extracellular matrix accumulation that is driven by myofibroblasts. The transcription factor megakaryoblastic leukemia-1 (MKL1) mediates myofibroblast differentiation in response to several profibrotic stimuli, but the role it plays in mediating pulmonary fibrosis has not been fully elucidated. In this study, we utilized mice that had a germline deletion of MKL1 (MKL1 (-,-)) to determine the role that MKL1 plays in the development of bleomycin-induced pulmonary fibrosis.
methodsBleomycin or normal saline were intratracheally delivered to 9 to 12 week old female MKL1 (+,+) and MKL1 (-,-) mice. Mice were assessed for weight loss and survival to 28 days. Inflammatory responses were assessed through bronchoalveolar lavage at days 3 and 7 post-treatment. The development of pulmonary fibrosis was characterized using hydroxyproline assay and histological staining. MKL1 (+,+) and MKL1 (-,-) mouse lung fibroblasts were isolated to compare morphologic, gene expression and functional differences.
resultsMKL1 (-,-) mice demonstrated increased survival, attenuated weight loss, and decreased collagen accumulation compared to wild-type animals 28-days after intratracheal instillation of bleomycin. Histological analysis demonstrated decreased trichrome, smooth muscle α-actin, and fibronectin staining in MKL1(-,-) mice compared to MKL1 (+,+) controls. Differential cell counts from bronchoalveolar lavage demonstrated that there was attenuated neutrophilia 3 days after bleomycin administration, but no difference at day 7. Isolated mouse lung fibroblasts from MKL1 (-,-) mice had decreased contractility and deposited less fibronectin matrix compared to wild-type controls, suggesting a defect in key remodeling functions.
conclusionsAltogether, these data demonstrate that MKL1 plays a significant role in mediating the fibrotic response to bleomycin injury. Loss of MKL1 attenuated early neutrophil influx, as well as myofibroblast-mediated remodeling. Targeting MKL1 activity may therefore be a useful strategy in treating pulmonary fibrosis.
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