ArticleAmerican journal of physiology. Lung cellular and molecular physiology2011
TGFβ signaling in lung epithelium regulates bleomycin-induced alveolar injury and fibroblast recruitment.
Article in American journal of physiology. Lung cellular and molecular physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 96 citations in OpenAlex.
- Emerging Concepts in Therapeutic Interventions for Idiopathic Pulmonary Fibrosis.Seminars in respiratory and critical care medicine · 2025Review
- Hypoxia-inducible factor 2 regulates alveolar regeneration after repetitive injury in three-dimensional cellular and in vivo models.Science translational medicine · 2025Article
- Chronic Kidney Disease-associated Lung Injury Is Mediated by Phosphate-induced MAPK/AKT Signaling.American journal of respiratory cell and molecular biology · 2024Article
- Dysregulated bidirectional epithelial-mesenchymal crosstalk: a core determinant of lung fibrosis progression.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Alveolar epithelial-to-mesenchymal transition in scleroderma interstitial lung disease: Technical challenges, available evidence and therapeutic perspectives.Journal of scleroderma and related disorders · 2024Review
- TGF-β controls alveolar type 1 epithelial cell plasticity and alveolar matrisome gene transcription in mice.The Journal of clinical investigation · 2024Article
- Persistent microbial infections and idiopathic pulmonary fibrosis - an insight intoFrontiers in cellular and infection microbiology · 2024Review
- Article
- Pulmonary Fibrosis as a Result of Acute Lung Inflammation: Molecular Mechanisms, Relevant In Vivo Models, Prognostic and Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Thromboxane-Prostanoid Receptor Signaling Drives Persistent Fibroblast Activation in Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2022Article
- Review
- Review
- Bimodal fibrosis in a novel mouse model of bleomycin-induced usual interstitial pneumonia.Life science alliance · 2022Article
- Review
- Cell tracing reveals the transdifferentiation fate of mouse lung epithelial cells during pulmonary fibrosisExperimental and therapeutic medicine · 2021Article
- Bleomycin induces fibrotic transformation of bone marrow stromal cells to treat height loss of intervertebral disc through the TGFβR1/Smad2/3 pathway.Stem cell research & therapy · 2021Article
- Autophagy inhibition-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in pulmonary fibrosis.Cell death & disease · 2019Article
- Paracrine signalling during ZEB1-mediated epithelial-mesenchymal transition augments local myofibroblast differentiation in lung fibrosis.Cell death and differentiation · 2019Article
- Epithelial-mesenchymal transition contributes to pulmonary fibrosis via aberrant epithelial/fibroblastic cross-talk.Journal of lung health and diseases · 2019Article
- The TRPV4-TAZ mechanotransduction signaling axis in matrix stiffness- and TGFβ1-induced epithelial-mesenchymal transition.Cellular and molecular bioengineering · 2019Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
The response of alveolar epithelial cells (AECs) to lung injury plays a central role in the pathogenesis of pulmonary fibrosis, but the mechanisms by which AECs regulate fibrotic processes are not well defined. We aimed to elucidate how transforming growth factor-β (TGFβ) signaling in lung epithelium impacts lung fibrosis in the intratracheal bleomycin model. Mice with selective deficiency of TGFβ receptor 2 (TGFβR2) in lung epithelium were generated and crossed to cell fate reporter mice that express β-galactosidase (β-gal) in cells of lung epithelial lineage. Mice were given intratracheal bleomycin (0.08 U), and the following parameters were assessed: AEC death by terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling assay, inflammation by total and differential cell counts from bronchoalveolar lavage, fibrosis by scoring of trichrome-stained lung sections, and total lung collagen content. Mice with lung epithelial deficiency of TGFβR2 had improved AEC survival, despite greater lung inflammation, after bleomycin administration. At 3 wk after bleomycin administration, mice with epithelial TGFβR2 deficiency showed a significantly attenuated fibrotic response in the lungs, as determined by semiquantitatve scoring and total collagen content. The reduction in lung fibrosis in these mice was associated with a marked decrease in the lung fibroblast population, both total lung fibroblasts and epithelial-to-mesenchymal transition-derived (S100A4(+)/β-gal(+)) fibroblasts. Attenuation of TGFβ signaling in lung epithelium provides protection from bleomycin-induced fibrosis, indicating a critical role for the epithelium in transducing the profibrotic effects of this cytokine.
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