ArticleRespiratory research2018
Differential effects of Nintedanib and Pirfenidone on lung alveolar epithelial cell function in ex vivo murine and human lung tissue cultures of pulmonary fibrosis.
Article in Respiratory research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04282902 (A Randomized, Open-label Study to Evaluate the Efficacy and Safety of Pirfenidone in Patients With Severe and Critical Novel Coronavirus Infection), which is not on this map. Cited by 88 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Randomized, Open-label Study to Evaluate the Efficacy and Safety of Pirfenidone in Patients With Severe and Critical Novel Coronavirus Infection
Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 137 citations in OpenAlex.
- Pooled it
- The role of fibrosis in endometriosis: a systematic review.Human reproduction update · 2024Pooled it
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Antifibrotic Drugs Regulate the Expression of Epithelial Sodium Channels in the Lungs.Advances in respiratory medicine · 2026Article
- 4D Time-lapse imaging of cell dynamics in human alveolar tissue by label-free higher harmonic generation microscopy.Journal of translational medicine · 2026Article
- Hydrogel-Embedded Precision-Cut Lung Slices Recapitulate Fibrotic Gene Expression and Enable Therapeutic Response Evaluation.bioRxiv : the preprint server for biology · 2026Article
- Parathyroid hormone-related protein is a therapeutic target in idiopathic pulmonary fibrosis.Signal transduction and targeted therapy · 2026Article
- Effects of Nintedanib on Orofacial Fibroblasts and Myoblasts.Biomolecules · 2026Article
- How the Fibrotic Lung Microenvironment Regulates Stem Cell Behavior: Immune Cues, Extracellular Matrix Remodeling, and Therapeutic Implications.Analytical cellular pathology (Amsterdam) · 2026Review
- Multi-omics to study chronic respiratory diseases and viral infections.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Targeting the epithelium in pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Emerging concepts and novel mechanisms in organ fibrosis.NPJ Regenerative medicine · 2025Article
- Insight into the pathogenesis of interstitial lung diseases and near-to-native lung fibrosis models.European journal of medical research · 2025Review
- A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.Nature biomedical engineering · 2025Article
- Article
- Label-free four-dimensional live imaging of immune-stromal interactions in human alveolar tissue using higher harmonic generation microscopy.The European respiratory journal · 2025Article
- LTI-03 peptide demonstrates anti-fibrotic activity iniScience · 2025Article
- Biomaterial-based 3D human lung models replicate pathological characteristics of early pulmonary fibrosis.Acta biomaterialia · 2025Article
- Bioinformatics-based identification of mirdametinib as a potential therapeutic target for idiopathic pulmonary fibrosis associated with endoplasmic reticulum stress.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Targeting cannabinoid receptor 1 for antagonism in pro-fibrotic alveolar macrophages mitigates pulmonary fibrosis.JCI insight · 2025Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Repetitive injury and reprogramming of the lung epithelium are thought to be critical drivers of disease progression, contributing to fibroblast activation, extracellular matrix remodeling, and subsequently loss of lung architecture and function. To date, Pirfenidone and Nintedanib are the only approved drugs known to decelerate disease progression, however, if and how these drugs affect lung epithelial cell function, remains largely unexplored.
methodsWe treated murine and human 3D ex vivo lung tissue cultures (3D-LTCs; generated from precision cut lung slices (PCLS)) as well as primary murine alveolar epithelial type II (pmATII) cells with Pirfenidone or Nintedanib. Murine 3D-LTCs or pmATII cells were derived from the bleomycin model of fibrosis. Early fibrotic changes were induced in human 3D-LTCs by a mixture of profibrotic factors. Epithelial and mesenchymal cell function was determined by qPCR, Western blotting, Immunofluorescent staining, and ELISA.
resultsLow μM concentrations of Nintedanib (1 μM) and mM concentrations of Pirfenidone (2.5 mM) reduced fibrotic gene expression including Collagen 1a1 and Fibronectin in murine and human 3D-LTCs as well as pmATII cells. Notably, Nintedanib stabilized expression of distal lung epithelial cell markers, especially Surfactant Protein C in pmATII cells as well as in murine and human 3D-LTCs.
conclusionsPirfenidone and Nintedanib exhibit distinct effects on murine and human epithelial cells, which might contribute to their anti-fibrotic action. Human 3D-LTCs represent a valuable tool to assess anti-fibrotic mechanisms of potential drugs for the treatment of IPF patients.
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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.