ArticleRespiratory research2016
Metformin attenuates lung fibrosis development via NOX4 suppression.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 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.
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Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 226 citations in OpenAlex.
- Pooled it
- Effectiveness and mechanism of metformin in animal models of pulmonary fibrosis: A preclinical systematic review and meta-analysis.Frontiers in pharmacology · 2022Pooled it
- Fibronectin's tensional state as a mechanical signature of fibrotic extracellular matrix in idiopathic pulmonary fibrosis models.Matrix biology plus · 2026Article
- Macrophage polarization plasticity in pulmonary fibrosis: a review from pathogenesis to therapeutic targeting.Inflammopharmacology · 2026Review
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Article
- Persistence of alveolar fibroblast-derived ADAMTS4+ cells in a preclinical model of delayed pulmonary fibrosis resolution.Nature communications · 2026Article
- Deficiency of GCN5 exacerbates pulmonary fibrosis by disrupting the LKB1-AMPK pathway.Cell communication and signaling : CCS · 2026Article
- Review
- Association of metformin with lung function decline and mortality in fibrotic interstitial lung disease: an observational cohort study.Respiratory research · 2026Observational
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Metformin attenuates fructose-induced pulmonary fibrosis, possibly through the involvement of the TRPC6 channel.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas · 2026Article
- Breaking barriers in pulmonary health of patients with metabolic diseases: senolytics and beyond.Frontiers in aging · 2026Review
- Idiopathic Pulmonary Fibrosis: A Comprehensive Review of Risk Factors, Genetics, Diagnosis, and Therapeutic Approaches.Biomedicines · 2026Review
- Metformin alleviates the progression of oral submucous fibrosis through downregulation of metastasis associated lung adenocarcinoma transcript 1 (MALAT1).Journal of dental sciences · 2026Article
- Altered Metabolism in Idiopathic Pulmonary Fibrosis.Journal of cellular physiology · 2025Review
- Reversal of Myofibroblast Apoptosis Resistance and Collagen Deposition by Phaseoloidin-Induced Autophagy Attenuates Pulmonary Fibrosis.Biomedicines · 2025Article
- Integrated spatial and single-cell transcriptomics reveal PAK kinase as a therapeutic target in fibroblastic foci and dense fibrosis of idiopathic pulmonary fibrosis.The European respiratory journal · 2025Article
- Hidden forces: the impact of cancer-associated fibroblasts on non-small cell lung cancer development and therapy.Journal of translational medicine · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
74 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
25 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAccumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)-β plays a key regulatory role in myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF-β-induced myofibroblast differentiation. Metformin is a biguanide antidiabetic medication and its pharmacological action is mediated through the activation of AMP-activated protein kinase (AMPK), which regulates not only energy homeostasis but also stress responses, including ROS. Therefore, we sought to investigate the inhibitory role of metformin in lung fibrosis development via modulating TGF-β signaling.
methodsTGF-β-induced myofibroblast differentiation in lung fibroblasts (LF) was used for in vitro models. The anti-fibrotic role of metfromin was examined in a bleomycin (BLM)-induced lung fibrosis model.
resultsWe found that TGF-β-induced myofibroblast differentiation was clearly inhibited by metformin treatment in LF. Metformin-mediated activation of AMPK was responsible for inhibiting TGF-β-induced NOX4 expression. NOX4 knockdown and N-acetylcysteine (NAC) treatment illustrated that NOX4-derived ROS generation was critical for TGF-β-induced SMAD phosphorylation and myofibroblast differentiation. BLM treatment induced development of lung fibrosis with concomitantly enhanced NOX4 expression and SMAD phosphorylation, which was efficiently inhibited by metformin. Increased NOX4 expression levels were also observed in FF of IPF lungs and LF isolated from IPF patients.
conclusionsThese findings suggest that metformin can be a promising anti-fibrotic modality of treatment for IPF affected by TGF-β.
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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.