ArticleAutophagy2017
Azithromycin attenuates myofibroblast differentiation and lung fibrosis development through proteasomal degradation of NOX4.
Article in Autophagy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 90 citations in OpenAlex.
- Antibiotic-Induced Pulmonary Fibrosis: National Database Analysis.Biomedicines · 2026Article
- TRIM36 inhibits lung fibroblast activation and pulmonary fibrosis through the degradation of phospho-AKT1.iScience · 2025Article
- A dual-targeting strategy to inhibit colorectal cancer liver metastasis via tumor cell ferroptosis and cancer-associated fibroblast reprogramming.Bioactive materials · 2025Article
- Single-Cell RNA Sequencing Identifies MMP11Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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- SIRT3/6/7: promising therapeutic targets for pulmonary fibrosis.Frontiers in cell and developmental biology · 2025Review
- Azithromycin Mitigates Tobacco Smoke-Induced Lung Senescence by Modulating the FOXO3A/CCND1 Signaling Pathway.International journal of chronic obstructive pulmonary disease · 2025Article
- Azithromycin Prevents Subglottic Stenosis in Mice.The Laryngoscope · 2025Article
- Targeting E3 ubiquitin ligases: a new frontier in idiopathic pulmonary fibrosis treatment.Frontiers in immunology · 2025Review
- Piezo channels modulate human lung fibroblast function.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- CircDCBLD2 alleviates liver fibrosis by regulating ferroptosis via facilitating STUB1-mediated PARK7 ubiquitination degradation.Journal of gastroenterology · 2024Article
- Effects ofAnimals : an open access journal from MDPI · 2024Article
- Abhd2, a Candidate Gene Regulating Airway Remodeling in COPD via TGF-β.International journal of chronic obstructive pulmonary disease · 2024Article
- Tissue fibrosis induced by radiotherapy: current understanding of the molecular mechanisms, diagnosis and therapeutic advances.Journal of translational medicine · 2023Review
- Macrolide antibiotics activate the integrated stress response and promote tumor proliferation.Cell stress · 2023Article
- Complex roles of TGF-β signaling pathways in lung development and bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2023Review
- Immunomodulatory role of azithromycin: Potential applications to radiation-induced lung injury.Frontiers in oncology · 2023Review
- Article
- Autophagy in pulmonary fibrosis: friend or foe?Genes & diseases · 2022Article
- Review
Corrections and comments
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Authors and funding
28 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of profibrotic myofibroblasts is involved in the process of fibrosis development during idiopathic pulmonary fibrosis (IPF) pathogenesis. TGFB (transforming growth factor β) is one of the major profibrotic cytokines for myofibroblast differentiation and NOX4 (NADPH oxidase 4) has an essential role in TGFB-mediated cell signaling. Azithromycin (AZM), a second-generation antibacterial macrolide, has a pleiotropic effect on cellular processes including proteostasis. Hence, we hypothesized that AZM may regulate NOX4 levels by modulating proteostasis machineries, resulting in inhibition of TGFB-associated lung fibrosis development. Human lung fibroblasts (LF) were used to evaluate TGFB-induced myofibroblast differentiation. With respect to NOX4 regulation via proteostasis, assays for macroautophagy/autophagy, the unfolded protein response (UPR), and proteasome activity were performed. The potential anti-fibrotic property of AZM was examined by using bleomycin (BLM)-induced lung fibrosis mouse models. TGFB-induced NOX4 and myofibroblast differentiation were clearly inhibited by AZM treatment in LF. AZM-mediated NOX4 reduction was restored by treatment with MG132, a proteasome inhibitor. AZM inhibited autophagy and enhanced the UPR. Autophagy inhibition by AZM was linked to ubiquitination of NOX4 via increased protein levels of STUB1 (STIP1 homology and U-box containing protein 1), an E3 ubiquitin ligase. An increased UPR by AZM was associated with enhanced proteasome activity. AZM suppressed lung fibrosis development induced by BLM with concomitantly reduced NOX4 protein levels and enhanced proteasome activation. These results suggest that AZM suppresses NOX4 by promoting proteasomal degradation, resulting in inhibition of TGFB-induced myofibroblast differentiation and lung fibrosis development. AZM may be a candidate for the treatment of the fibrotic lung disease IPF.
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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.