ArticlePloS one2014
Intratracheal instillation of high dose adenoviral vectors is sufficient to induce lung injury and fibrosis in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Integrins and pulmonary fibrosis: Pathogenic roles and therapeutic opportunities.Biomolecules & biomedicine · 2025Review
- Intratracheal instillation of RSV is superior to intranasal inoculation as a model method inducing critical immune cell infiltration.Scientific reports · 2025Article
- CD206 and dust particles are prognostic biomarkers of progressive fibrosing interstitial lung disease associated with air pollutant exposure.Scientific reports · 2025Article
- Animal models of acute exacerbation of pulmonary fibrosis.Respiratory research · 2023Review
- Tyrosine-Mutant AAV8 Vector Mediated Efficient and Safe Gene Transfer of Pigment Epithelium-Derived Factor to Mouse Lungs.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2023Article
- Anti-Inflammatory and Anti-Fibrotic Effect of Immortalized Mesenchymal-Stem-Cell-Derived Conditioned Medium on Human Lung Myofibroblasts and Epithelial Cells.International journal of molecular sciences · 2022Article
- The Crucial Role of NLRP3 Inflammasome in Viral Infection-Associated Fibrosing Interstitial Lung Diseases.International journal of molecular sciences · 2021Review
- A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma.Cell reports methods · 2021Article
- The Inflammatory and Fibrotic Patterns of Hepatic Stellate Cells Following Coagulation Factors (VII or X)-Shielded Adenovirus Infection.Current microbiology · 2021Article
- Pulmonary Emphysema Cross-Linking with Pulmonary Fibrosis and Vice Versa: a Non-usual Experimental Intervention with Elastase and Bleomycin.Inflammation · 2017Article
- Role of Microbial Agents in Pulmonary Fibrosis .The Yale journal of biology and medicine · 2017Review
- Linking bronchopulmonary dysplasia to adult chronic lung diseases: role of WNT signaling.Molecular and cellular pediatrics · 2016Review
- Suppression of von Hippel-Lindau Protein in Fibroblasts Protects against Bleomycin-Induced Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleReplication deficient adenoviruses (Ad) vectors are common tools in gene therapy. Since Ad vectors are known to activate innate and adaptive immunity, we investigated whether intratracheal administration of Ad vectors alone is sufficient to induce lung injury and pulmonary fibrosis.
methodsWe instilled Ad viruses ranging from 107 to 1.625×109 ifu/mouse as well as the same volume of PBS and bleomycin. 14 and 21 days after administration, we collected bronchoalveolar lavage fluid (BALF) and mouse lung tissues. We measured the protein concentration, total and differential cell counts, and TGF-β1 production, performed Trichrome staining and Sircol assay, determined gene and protein levels of profibrotic cytokines, MMPs, and Wnt signaling proteins, and conducted TUNEL staining and co-immunofluorescence for GFP and α-SMA staining.
resultsInstillation of high dose Ad vectors (1.625×109 ifu/mouse) into mouse lungs induced high levels of protein content, inflammatory cells, and TGF-β1 in BALF, comparable to those in bleomycin-instilled lungs. The collagen content and mRNA levels of Col1a1, Col1a2, PCNA, and α-SMA were also increased in the lungs. Instillation of both bleomycin and Ad vectors increased expression levels of TNFα and IL-1β but not IL-10. Instillation of bleomycin but not Ad increased the expression of IL-1α, IL-13 and IL-16. Treatment with bleomycin or Ad vectors increased expression levels of integrin α1, α5, and αv, MMP9, whereas treatment with bleomycin but not Ad vectors induced MMP2 expression levels. Both bleomycin and Ad vectors induced mRNA levels of Wnt2, 2b, 5b, and Lrp6. Intratracheal instillation of Ad viruses also induced DNA damages and Ad viral infection-mediated fibrosis is not limited to the infection sites.
conclusionsOur results suggest that administration of Ad vectors induces an inflammatory response, lung injury, and pulmonary fibrosis in a dose dependent manner.
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