ArticleAmerican journal of respiratory and critical care medicine2010
Targeted injury of type II alveolar epithelial cells induces pulmonary fibrosis.
Article in American journal of respiratory and critical care medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 277 papers, 1 of them a synthesis that pooled it.
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Who cites it
277 citing papers in PubMed, 1 synthesis or guideline pooled it, 485 citations in OpenAlex.
- Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application.Stem cell research & therapy · 2021Pooled it
- Alveolar epithelial depletion of βPAK-interacting exchange factor drives spontaneous pulmonary fibrosis by impairing stemness.Signal transduction and targeted therapy · 2026Article
- Engineered exosomes encapsulated miR-218-5p alleviate the progression of PMRedox biology · 2026Article
- Advances in our understanding of distal progenitors in idiopathic pulmonary fibrosis: implications for novel therapeutics.The European respiratory journal · 2026Review
- Dual-mechanism inhalable nanocomposite restores the alveolar mucus barrier and enables deep-lesion delivery for synergistic treatment of pulmonary fibrosis.Journal of nanobiotechnology · 2026Article
- Antifibrotic Effects ofInternational journal of molecular sciences · 2026Article
- Engraftment of wild-type alveolar type II epithelial cells in surfactant protein C deficient mice.NPJ Regenerative medicine · 2026Article
- Transcriptomic Analysis of the Antiviral Responses in Ovine Type II Alveolar Epithelial Cells During Early Stage of Bluetongue Virus Infection.Animals : an open access journal from MDPI · 2026Article
- GDF15 participates in epithelial cell senescence in radiation-induced lung injury through the ERK1/2-p16 signaling pathway.PloS one · 2026Article
- Magnesium, Zinc and Copper in Lung Fibrosis: A Narrative Review.Medicina (Kaunas, Lithuania) · 2025Review
- Immunopathogenic Mechanisms in Connective Tissue Disease-Associated Interstitial Lung Disease: Incessant Loop of Immunity to Fibrosis.International journal of molecular sciences · 2025Review
- Mitochondrial components secretion in extracellular vesicles promotes alveolar epithelial mitochondrial quality control.Nature communications · 2025Article
- Homocysteine Exacerbates Pulmonary Fibrosis via Orchestrating Syntaxin 17 Homocysteinylation of Alveolar Type II Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Fzd2 orchestrates canonical and non-canonical Wnt signaling to regulate lung development and fibrosis.Cell communication and signaling : CCS · 2025Article
- YBX1 regulation of alveolar type II epithelial cells in idiopathic pulmonary fibrosis: mechanistic insights and small-molecule drug screening.Journal of translational medicine · 2025Article
- Modeling functional responses to pollutant exposure using modular hydrogel supported vascularized alveolosphere-on-a-chip.Biomaterials science · 2025Article
- STAT6 Activation Exacerbates Ferroptosis in Airway Epithelium by Inhibiting PRKN-Mediated Mitophagy in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Exploring the Cellular and Molecular Landscape of Idiopathic Pulmonary Fibrosis: Integrative Multi-Omics and Single-Cell Analysis.Biomedicines · 2025Article
- Targeting Plasminogen Activator Inhibitor-1 with a Novel Small Molecule Inhibitor Attenuates Lung Fibrosis.Research square · 2025Article
- Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis.JCI insight · 2025Article
217 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
rationaleIneffective repair of a damaged alveolar epithelium has been postulated to cause pulmonary fibrosis. In support of this theory, epithelial cell abnormalities, including hyperplasia, apoptosis, and persistent denudation of the alveolar basement membrane, are found in the lungs of humans with idiopathic pulmonary fibrosis and in animal models of fibrotic lung disease. Furthermore, mutations in genes that affect regenerative capacity or that cause injury/apoptosis of type II alveolar epithelial cells have been identified in familial forms of pulmonary fibrosis. Although these findings are compelling, there are no studies that demonstrate a direct role for the alveolar epithelium or, more specifically, type II cells in the scarring process.
objectivesTo determine if a targeted injury to type II cells would result in pulmonary fibrosis.
methodsA transgenic mouse was generated to express the human diphtheria toxin receptor on type II alveolar epithelial cells. Diphtheria toxin was administered to these animals to specifically target the type II epithelium for injury. Lung fibrosis was assessed by histology and hydroxyproline measurement. MEASUREMENTS AND MAIN
resultsTransgenic mice treated with diphtheria toxin developed an approximately twofold increase in their lung hydroxyproline content on Days 21 and 28 after diphtheria toxin treatment. The fibrosis developed in conjunction with type II cell injury. Histological evaluation revealed diffuse collagen deposition with patchy areas of more confluent scarring and associated alveolar contraction.
conclusionsThe development of lung fibrosis in the setting of type II cell injury in our model provides evidence for a causal link between the epithelial defects seen in idiopathic pulmonary fibrosis and the corresponding areas of scarring.
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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.