ArticleThe Journal of biological chemistry2014
Influenza promotes collagen deposition via αvβ6 integrin-mediated transforming growth factor β activation.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 54 citations in OpenAlex.
- Article
- Exacerbated Hepatic Stress and Systemic Metabolic Disruption Driven by SARS-CoV-2 P.1 Variant in K18-hACE2 Mice.Immunity, inflammation and disease · 2026Article
- Pirfenidone Mitigates Transforming Growth Factor-β-induced Inflammation after Viral Infection.American journal of respiratory cell and molecular biology · 2025Article
- Early detection of cytokine storm and IgG levels to predict and prevent severe COVID-19 infection.Journal of family medicine and primary care · 2025Article
- Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities.Biomolecules & biomedicine · 2025Review
- Prim-O-glucosylcimifugin alleviates influenza virus-induced pneumonia in mice by inhibiting the TGF-β1/PI3KCD/MSK2/RELA signalling pathway.Archives of virology · 2024Article
- Distinct pulmonary and systemic effects of dexamethasone in severe COVID-19.Nature communications · 2024Article
- Chloride Intracellular Channel Protein 1 (CLIC1) Is a Critical Host Cellular Factor for Influenza A Virus Replication.Viruses · 2024Article
- Toll-like receptors and integrins crosstalk.Frontiers in immunology · 2024Review
- Clinicopathological Outlines of Post-COVID-19 Pulmonary Fibrosis Compared with Idiopathic Pulmonary Fibrosis.Biomedicines · 2023Review
- The IL-33:ST2 axis is unlikely to play a central fibrogenic role in idiopathic pulmonary fibrosis.Respiratory research · 2023Article
- Immune-mediated lung diseases: A narrative review.Frontiers in medicine · 2023Review
- Interstitial Pulmonary Fibrosis and Extensive Dendriform Ossification with Persistent Viral Load: A Rare Presentation of Post-COVID-19 Condition in Need of Lung Transplantation.Pathobiology : journal of immunopathology, molecular and cellular biology · 2023Article
- Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract.Nature reviews. Microbiology · 2021Review
- COVID-19 and pulmonary fibrosis: A potential role for lung epithelial cells and fibroblasts.Immunological reviews · 2021Review
- Post-COVID lung fibrosis: The tsunami that will follow the earthquake.Lung India : official organ of Indian Chest Society · 2021Review
- Myofibroblast TGF-β Activation Measurement In Vitro.Methods in molecular biology (Clifton, N.J.) · 2021Article
- You Say You Want a Resolution (of Fibrosis).American journal of respiratory cell and molecular biology · 2020Review
- Demystifying pulmonary fibrosis.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Hydroxychloroquine in rheumatic autoimmune disorders and beyond.EMBO molecular medicine · 2020Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Influenza infection exacerbates chronic pulmonary diseases, including idiopathic pulmonary fibrosis. A central pathway in the pathogenesis of idiopathic pulmonary fibrosis is epithelial injury leading to activation of transforming growth factor β (TGFβ). The mechanism and functional consequences of influenza-induced activation of epithelial TGFβ are unclear. Influenza stimulates toll-like receptor 3 (TLR3), which can increase RhoA activity, a key event prior to activation of TGFβ by the αvβ6 integrin. We hypothesized that influenza would stimulate TLR3 leading to activation of latent TGFβ via αvβ6 integrin in epithelial cells. Using H1152 (IC50 6.1 μm) to inhibit Rho kinase and 6.3G9 to inhibit αvβ6 integrins, we demonstrate their involvement in influenza (A/PR/8/34 H1N1) and poly(I:C)-induced TGFβ activation. We confirm the involvement of TLR3 in this process using chloroquine (IC50 11.9 μm) and a dominant negative TLR3 construct (pZERO-hTLR3). Examination of lungs from influenza-infected mice revealed augmented levels of collagen deposition, phosphorylated Smad2/3, αvβ6 integrin, and apoptotic cells. Finally, we demonstrate that αvβ6 integrin-mediated TGFβ activity following influenza infection promotes epithelial cell death in vitro and enhanced collagen deposition in vivo and that this response is diminished in Smad3 knock-out mice. These data show that H1N1 and poly(I:C) can induce αvβ6 integrin-dependent TGFβ activity in epithelial cells via stimulation of TLR3 and suggest a novel mechanism by which influenza infection may promote collagen deposition in fibrotic lung disease.
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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.