ArticleAmerican journal of respiratory cell and molecular biology2012
Influenza induces endoplasmic reticulum stress, caspase-12-dependent apoptosis, and c-Jun N-terminal kinase-mediated transforming growth factor-β release in lung epithelial cells.
Article in American journal of respiratory cell and molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 128 citations in OpenAlex.
- Lung fibrosis-associated surfactant protein A1 and C variants induce latent transforming growth factor β1 secretion in lung epithelial cells.The Journal of biological chemistry · 2013Trial
- Don't Stress: We're One Step Closer to Host-Directed Therapy for Influenza.American journal of respiratory cell and molecular biology · 2026Article
- Orchestrating immunopathology: the spectrum of programmed cell death pathways co-opted by influenza a virus in pulmonary immunity.Frontiers in immunology · 2026Review
- FAK-dependent activation of src family kinase member BLK contributed to endometrial fibrosis via endoplasmic reticulum stress.Cell & bioscience · 2025Article
- Activation of the endoplasmic reticulum stress regulator IRE1α compromises pulmonary host defenses.Cell reports · 2025Article
- Revisiting pulmonary fibrosis: inflammatory dynamics of the lipofibroblast-to-inflammatory lipofibroblast-to-activated myofibroblast reversible switch.Frontiers in immunology · 2025Review
- Lactate activates ER stress to promote alveolar epithelial cells apoptosis in pulmonary fibrosis.Respiratory research · 2024Article
- The protein disulfide isomerase A3 and osteopontin axis promotes influenza-induced lung remodelling.British journal of pharmacology · 2024Article
- Influenza, SARS-CoV-2, and Their Impact on Chronic Lung Diseases and Fibrosis: Exploring Therapeutic Options.The American journal of pathology · 2024Review
- The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.International journal of molecular sciences · 2024Review
- The H9N2 avian influenza virus increases APEC adhesion to oviduct epithelia by viral NS1 protein-mediated activation of the TGF-β pathway.Journal of virology · 2024Article
- Article
- Aromatic amino acid metabolites alter interferon signaling and influenza pathogenesis.Frontiers in molecular biosciences · 2023Article
- DT-010 Exerts Cardioprotective Effects by Regulating the Crosstalk between the AMPK/PGC-1Cardiovascular therapeutics · 2023Article
- Microvascular lung injury and endoplasmic reticulum stress in systemic lupus erythematosus-associated alveolar hemorrhage and pulmonary vasculitis.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- ZC3H4 regulates infiltrating monocytes, attenuating pulmonary fibrosis through IL-10.Respiratory research · 2022Article
- Tauroursodeoxycholic acid inhibits TGF-β1-induced renal fibrosis markers in cultured renal mesangial cells by regulating endoplasmic reticulum stress.Experimental and therapeutic medicine · 2022Article
- Regulatory effects of Trichinella spiralis and a serine protease inhibitor on the endoplasmic reticulum stress response of intestinal epithelial cells.Veterinary research · 2022Article
- ERp57/PDIA3: new insight.Cellular & molecular biology letters · 2022Review
- Protein Disulfide Isomerase A3 Regulates Influenza Neuraminidase Activity and Influenza Burden in the Lung.International journal of molecular sciences · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Influenza A virus (IAV) infection is known to induce endoplasmic reticulum (ER) stress, Fas-dependent apoptosis, and TGF-β production in a variety of cells. However, the relationship between these events in murine primary tracheal epithelial cells (MTECS), which are considered one of the primary sites of IAV infection and replication, is unclear. We show that IAV infection induced ER stress marker activating transcription factor-6 and endoplasmic reticulum protein 57-kD (ERp57), but not C/EBP homologous protein (CHOP). In contrast, the ER stress inducer thapsigargin (THP) increased CHOP. IAV infection activated caspases and apoptosis, independently of Fas and caspase-8, in MTECs. Instead, apoptosis was mediated by caspase-12. A decrease in ERp57 attenuated the IAV burden and decreased caspase-12 activation and apoptosis in epithelial cells. TGF-β production was enhanced in IAV-infected MTECs, compared with THP or staurosporine. IAV infection caused the activation of c-Jun N-terminal kinase (JNK). Furthermore, IAV-induced TGF-β production required the presence of JNK1, a finding that suggests a role for JNK1 in IAV-induced epithelial injury and subsequent TGF-β production. These novel findings suggest a potential mechanistic role for a distinct ER stress response induced by IAV, and a profibrogenic/repair response in contrast to other pharmacological inducers of ER stress. These responses may also have a potential role in acute lung injury, fibroproliferative acute respiratory distress syndrome, and the recently identified H1N1 influenza-induced exacerbations of chronic obstructive pulmonary disease (Wedzicha JA. Proc Am Thorac Soc 2004;1:115-120) and idiopathic pulmonary fibrosis (Umeda Y, et al. Int Med 2010;49:2333-2336).
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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.