ArticleAmerican journal of respiratory cell and molecular biology2020
Bleomycin Induces Drug Efflux in Lungs. A Pitfall for Pharmacological Studies of Pulmonary Fibrosis.
Article in American journal of respiratory cell and molecular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- Nintedanib Lacks Efficacy in a Spirometry-Confirmed and Bleomycin-Induced Mouse Model of Idiopathic Pulmonary Fibrosis.Basic & clinical pharmacology & toxicology · 2026Article
- Testing the Possible Protective Effect of Ivermectin on Bleomycin-Induced Pulmonary Fibrosis in Albino Rats: Histological and Immunohistochemical Study.Medicina (Kaunas, Lithuania) · 2026Article
- Exosomes from Human Embryonic Stem Cell-Derived Mesenchymal Stem Cells Protect Lung Epithelium and Attenuate Fibrosis.International journal of stem cells · 2026Article
- Investigation of the Protective Effect of Betaine in an Experimental Pulmonary Fibrosis Model Induced by Intratracheal Administration of Bleomycin.Journal of clinical practice and research · 2025Article
- Anandamide Is a Potential Blood Biomarker of Hermansky-Pudlak Syndrome Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2025Article
- Mechanisms of Bleomycin-induced Lung Fibrosis: A Review of Therapeutic Targets and Approaches.Cell biochemistry and biophysics · 2024Review
- A mouse model of progressive lung fibrosis with cutaneous involvement induced by a combination of oropharyngeal and osmotic minipump bleomycin delivery.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Anandamide is an Early Blood Biomarker of Hermansky-Pudlak Syndrome Pulmonary Fibrosis.medRxiv : the preprint server for health sciences · 2024Article
- An Integrative Multiomics Framework for Identification of Therapeutic Targets in Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- ATP12A: Connecting Mucus and Fibrosis in Idiopathic Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2023Article
- Animal models of drug-induced pulmonary fibrosis: an overview of molecular mechanisms and characteristics.Cell biology and toxicology · 2022Review
- Article
- The normal and fibrotic mouse lung classified by spatial proteomic analysis.Scientific reports · 2022Article
- Progressive pulmonary fibrosis in a murine model of Hermansky-Pudlak syndrome.Respiratory research · 2022Article
- Chronic and Binge Alcohol Ingestion Increases Truncated Oxidized Phosphatidylcholines in Mice Lungs Due to Increased Oxidative Stress.Frontiers in physiology · 2022Article
- CBClinical and translational medicine · 2021Article
- Update in Interstitial Lung Disease 2020.American journal of respiratory and critical care medicine · 2021Review
- Toll-Interacting Protein in Pulmonary Diseases. Abiding by the Goldilocks Principle.American journal of respiratory cell and molecular biology · 2021Review
- Peripheral Hybrid CBFrontiers in endocrinology · 2021Article
- Extracellular CIRP Induces an Inflammatory Phenotype in Pulmonary FibroblastsFrontiers in immunology · 2021Article
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10 authors at 2 institutions in 1 country.
Funding
Abstract
ATP-binding cassette (ABC) transporters are evolutionarily conserved membrane proteins that pump a variety of endogenous substrates across cell membranes. Certain subfamilies are known to interact with pharmaceutical compounds, potentially influencing drug delivery and treatment efficacy. However, the role of drug resistance-associated ABC transporters has not been examined in idiopathic pulmonary fibrosis (IPF) or its animal model: the bleomycin (BLM)-induced murine model. Here, we investigate the expression of two ABC transporters, P-gp (permeability glycoprotein) and BCRP (breast cancer resistance protein), in human IPF lung tissue and two different BLM-induced mouse models of pulmonary fibrosis. We obtained human IPF specimens from patients during lung transplantation and administered BLM to male C57BL/6J mice either by oropharyngeal aspiration (1 U/kg) or subcutaneous osmotic infusion (100 U/kg over 7 d). We report that P-gp and BCRP expression in lungs of patients with IPF was comparable to controls. However, murine lungs expressed increased levels of P-gp and BCRP after oropharyngeal and subcutaneous BLM administration. We localized this upregulation to multiple pulmonary cell types, including alveolar fibroblasts, endothelial cells, and type 2 epithelial cells. Functionally, this effect reduced murine lung exposure to nintedanib, a U.S. Food and Drug Administration-approved IPF therapy known to be a P-gp substrate. The study reveals a discrepancy between IPF pathophysiology and the common animal model of lung fibrosis. BLM-induced drug efflux in the murine lungs may present an uncontrolled confounding variable in the preclinical study of IPF drug candidates, and these findings will facilitate disease model validation and enhance new drug discoveries that will ultimately improve patient outcomes.
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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.