ArticleProceedings of the National Academy of Sciences of the United States of America2015
Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle inducing a higher fibrotic response via TGF-β signaling.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 101 citations in OpenAlex.
- Organelle Crosstalk and Metabolic Reprogramming in Idiopathic Pulmonary Fibrosis: Mechanisms and Therapeutic Implications.Cell biochemistry and function · 2026Review
- IL1RAP Antibody-Drug Conjugates Potently Target Primary and Metastatic Diseases in Multiple Oncofusion-Driven Cancers.Cancer discovery · 2026Article
- Peroxisomes in Liver Diseases: From Metabolite Quality Control to Inter-Organelle and Inter-Organ Signaling.Biomolecules · 2026Review
- Review
- Dual-mechanism inhalable nanocomposite restores the alveolar mucus barrier and enables deep-lesion delivery for synergistic treatment of pulmonary fibrosis.Journal of nanobiotechnology · 2026Article
- Decoding organ fibrosis: mechanistic insights and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Diosgenin mitigates laser-induced choroidal neovascularization by suppressing the endothelial-to-mesenchymal transition via the TGF-β/Smad and MAPKs signaling pathways.American journal of translational research · 2026Article
- Alteration of Lipid Metabolism in Patients with IPF and Its Association with Disease Severity and Prognosis: A Case-Control Study.International journal of molecular sciences · 2025Observational
- Identification of shared important genes associated with ferroptosis across different etiologies of acute lung injury.Scientific reports · 2025Article
- Mesenchymal stem cells alleviate pulmonary fibrosis and gut microbiota dysbiosis in systemic sclerosis.Frontiers in microbiology · 2025Article
- Selective activation of PPARα by pemafibrate mitigates peritoneal inflammation and fibrosis through suppression of NLRP3 inflammasome and modulation of inflammation.Scientific reports · 2024Article
- It takes two peroxisome proliferator-activated receptors (PPAR-β/δ and PPAR-γ) to tango idiopathic pulmonary fibrosis.Respiratory research · 2024Article
- Idiopathic pulmonary fibrosis (IPF): disease pathophysiology, targets, and potential therapeutic interventions.Molecular and cellular biochemistry · 2024Review
- Potential Role of Macrophage Polarization in the Progression of Hunner-Type Interstitial Cystitis.International journal of molecular sciences · 2024Article
- Promising Therapeutic Treatments for Cardiac Fibrosis: Herbal Plants and Their Extracts.Cardiology and therapy · 2023Review
- Oxidative Stress and Lung Fibrosis: Towards an Adverse Outcome Pathway.International journal of molecular sciences · 2023Review
- The mRNA-binding protein DDX3 mediates TGF-β1 upregulation of translation and promotes pulmonary fibrosis.JCI insight · 2023Article
- Transforming Growth Factor-β1 Regulates Peroxisomal Genes/Proteins via Smad Signaling in Idiopathic Pulmonary Fibrosis Fibroblasts and Transgenic Mouse Models.The American journal of pathology · 2023Article
- Drugs against metabolic diseases as potential senotherapeutics for aging-related respiratory diseases.Frontiers in endocrinology · 2023Review
- Direct Stochastic Optical Reconstruction Microscopy (dSTORM) of Peroxisomes.Methods in molecular biology (Clifton, N.J.) · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiopathic pulmonary fibrosis (IPF) is a devastating disease, and its pathogenic mechanisms remain incompletely understood. Peroxisomes are known to be important in ROS and proinflammatory lipid degradation, and their deficiency induces liver fibrosis. However, altered peroxisome functions in IPF pathogenesis have never been investigated. By comparing peroxisome-related protein and gene expression in lung tissue and isolated lung fibroblasts between human control and IPF patients, we found that IPF lungs exhibited a significant down-regulation of peroxisomal biogenesis and metabolism (e.g., PEX13p and acyl-CoA oxidase 1). Moreover, in vivo the bleomycin-induced down-regulation of peroxisomes was abrogated in transforming growth factor beta (TGF-β) receptor II knockout mice indicating a role for TGF-β signaling in the regulation of peroxisomes. Furthermore, in vitro treatment of IPF fibroblasts with the profibrotic factors TGF-β1 or tumor necrosis factor alpha (TNF-α) was found to down-regulate peroxisomes via the AP-1 signaling pathway. Therefore, the molecular mechanisms by which reduced peroxisomal functions contribute to enhanced fibrosis were further studied. Direct down-regulation of PEX13 by RNAi induced the activation of Smad-dependent TGF-β signaling accompanied by increased ROS production and resulted in the release of cytokines (e.g., IL-6, TGF-β) and excessive production of collagen I and III. In contrast, treatment of fibroblasts with ciprofibrate or WY14643, PPAR-α activators, led to peroxisome proliferation and reduced the TGF-β-induced myofibroblast differentiation and collagen protein in IPF cells. Taken together, our findings suggest that compromised peroxisome activity might play an important role in the molecular pathogenesis of IPF and fibrosis progression, possibly by exacerbating pulmonary inflammation and intensifying the fibrotic response in the patients.
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