ArticleAmerican journal of respiratory and critical care medicine2016
Membrane-anchored Serine Protease Matriptase Is a Trigger of Pulmonary Fibrogenesis.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 50 citations in OpenAlex.
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- PAR2 Activation on Human Kidney Tubular Epithelial Cells Induces Tissue Factor Synthesis, That Enhances Blood Clotting.Frontiers in physiology · 2021Article
- Myeloid Protease-Activated Receptor-2 Contributes to Influenza A Virus Pathology in Mice.Frontiers in immunology · 2021Article
- Traditional Uses, Pharmacological Effects, and Molecular Mechanisms of Licorice in Potential Therapy of COVID-19.Frontiers in pharmacology · 2021Review
- Iripin-3, a New Salivary Protein Isolated FromFrontiers in immunology · 2021Article
- Proteolytic cleavage of Podocin by Matriptase exacerbates podocyte injury.The Journal of biological chemistry · 2020Article
- Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation.Critical care explorations · 2020Article
- Membrane-anchored serine proteases as regulators of epithelial function.Biochemical Society transactions · 2020Review
- Protease-activated receptor-2 accelerates intestinal tumor formation through activation of nuclear factor-κB signaling and tumor angiogenesis in ApcCancer science · 2020Article
- In Vivo Endomicroscopy of Lung Injury and Repair in ARDS: Potential Added Value to Current Imaging.Journal of clinical medicine · 2019Review
- Proteases: Pivot Points in Functional Proteomics.Methods in molecular biology (Clifton, N.J.) · 2019Review
- CCAAT/enhancer binding protein delta (C/EBPδ) deficiency does not affect bleomycin-induced pulmonary fibrosis.Journal of clinical and translational research · 2018Article
- Signaling Crosstalk of TGF-β/ALK5 and PAR2/PAR1: A Complex Regulatory Network Controlling Fibrosis and Cancer.International journal of molecular sciences · 2018Review
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Authors and funding
16 authors at 8 institutions in 6 countries.
Funding
Abstract
rationaleIdiopathic pulmonary fibrosis (IPF) is a devastating disease that remains refractory to current therapies.
objectivesTo characterize the expression and activity of the membrane-anchored serine protease matriptase in IPF in humans and unravel its potential role in human and experimental pulmonary fibrogenesis.
methodsMatriptase expression was assessed in tissue specimens from patients with IPF versus control subjects using quantitative reverse transcriptase-polymerase chain reaction, immunohistochemistry, and Western blotting, while matriptase activity was monitored by fluorogenic substrate cleavage. Matriptase-induced fibroproliferative responses and the receptor involved were characterized in human primary pulmonary fibroblasts by Western blot, viability, and migration assays. In the murine model of bleomycin-induced pulmonary fibrosis, the consequences of matriptase depletion, either by using the pharmacological inhibitor camostat mesilate (CM), or by genetic down-regulation using matriptase hypomorphic mice, were characterized by quantification of secreted collagen and immunostainings. MEASUREMENTS AND MAIN
resultsMatriptase expression and activity were up-regulated in IPF and bleomycin-induced pulmonary fibrosis. In cultured human pulmonary fibroblasts, matriptase expression was significantly induced by transforming growth factor-β. Furthermore, matriptase elicited signaling via protease-activated receptor-2 (PAR-2), and promoted fibroblast activation, proliferation, and migration. In the experimental bleomycin model, matriptase depletion, by the pharmacological inhibitor CM or by genetic down-regulation, diminished lung injury, collagen production, and transforming growth factor-β expression and signaling.
conclusionsThese results implicate increased matriptase expression and activity in the pathogenesis of pulmonary fibrosis in human IPF and in an experimental mouse model. Overall, targeting matriptase, or treatment by CM, which is already in clinical use for other diseases, may represent potential therapies for IPF.
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