ReviewAmerican journal of physiology. Lung cellular and molecular physiology2013
TGF-β-Smad3 signaling in emphysema and pulmonary fibrosis: an epigenetic aberration of normal development?
Review in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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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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.
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Who cites it
54 citing papers in PubMed, 115 citations in OpenAlex.
- Cigarette smoke enhances proliferation and extracellular matrix deposition by human fetal airway smooth muscle.American journal of physiology. Lung cellular and molecular physiology · 2014Trial
- Epigenetic dysregulation of IRF9 drives excessive interferon signaling in COPD.EMBO molecular medicine · 2026Article
- The Regulatory Mechanism of MicroRNA-144-3p on Damage to Endometrial Epithelial Cells Exposed to Copper Ions In Vitro.Current medical science · 2025Article
- Apigenin's Influence on Inflammatory and Epigenetic Responses in Rat Lungs After Radiotherapy.Current radiopharmaceuticals · 2025Article
- Lung Transcriptomics Link Emphysema to Barrier Dysfunction and Macrophage Subpopulations.American journal of respiratory and critical care medicine · 2025Article
- The role and regulation of SIRT1 in pulmonary fibrosis.Molecular biology reports · 2024Review
- Huangqi-Danshen Decoction Against Renal Fibrosis in UUO Mice via TGF-β1 Induced Downstream Signaling Pathway.Drug design, development and therapy · 2024Article
- Paroxetine protects against bleomycin-induced pulmonary fibrosis by blocking GRK2/Smad3 pathway.Aging · 2023Article
- Recombinant Human HAPLN1 Mitigates Pulmonary Emphysema by Increasing TGF-β Receptor I and Sirtuins Levels in Human Alveolar Epithelial Cells.Molecules and cells · 2023Article
- Syndrome of Combined Pulmonary Fibrosis and Emphysema: An Official ATS/ERS/JRS/ALAT Research Statement.American journal of respiratory and critical care medicine · 2022Article
- Targeting non-coding RNA H19: A potential therapeutic approach in pulmonary diseases.Frontiers in pharmacology · 2022Review
- Hypoxia-induced preadipocyte factor 1 expression in human lung fibroblasts through ERK/PEA3/c-Jun pathway.Molecular medicine (Cambridge, Mass.) · 2021Article
- APOBEC1 complementation factor facilitates cell migration by promoting nucleus translocation of SMAD3 in renal cell carcinoma cells.In vitro cellular & developmental biology. Animal · 2021Article
- Inhibition of Sirt2 Alleviates Fibroblasts Activation and Pulmonary FibrosisFrontiers in pharmacology · 2021Article
- Gastrin-releasing peptide induces fibrotic response in MRC5s and proliferation in A549s.Cell communication and signaling : CCS · 2020Article
- Long Noncoding RNA FENDRR Exhibits Antifibrotic Activity in Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2020Article
- Effects of tetrandrine combined with acetylcysteine on exercise tolerance, pulmonary function and serum TNF-β1 and MMP-7 in silicosis patients.Experimental and therapeutic medicine · 2020Article
- Caveolin-1 scaffolding domain peptide prevents hyperoxia-induced airway remodeling in a neonatal mouse model.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- Knockdown of Long Noncoding RNA H19 Represses the Progress of Pulmonary Fibrosis through the Transforming Growth Factor β/Smad3 Pathway by Regulating MicroRNA 140.Molecular and cellular biology · 2019Article
- Integrative Genomics Analysis Identifies ACVR1B as a Candidate Causal Gene of Emphysema Distribution.American journal of respiratory cell and molecular biology · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
It is well accepted that TGF-β signaling has critical functional roles in lung development, injury, and repair. We showed previously that null mutation of Smad3, a critical node in the TGF-β pathway, protects mice against fibrosis induced by bleomycin. However, more recently we noticed that abnormal alveolarization also occurs in Smad3-deficient mice and that this is followed by progressive emphysema-like alveolar wall destruction mediated by MMP9. We now know that Smad3 cooperates with c-Jun to synergistically regulate a protein deacetylase SIRT1, by binding to an AP-1 site in the SIRT1 promoter. Consistently, Smad3 knockout lung at postnatal day 28 had reduced SIRT1 expression, which in turn resulted in increased histone acetylation at the binding sites of the transcription factors AP-1, NF-κB, and Pea3 on the MMP9 promoter, as well as increased acetylation of NF-κB. Thus, upon TGF-β activation, phosphorylated Smad3 can be translocated into the nucleus with Smad4, whereat Smad3 in turn collaborates with c-Jun to activate SIRT1 transcription. SIRT1 can deacetylate NF-κB at lysine 30, as well as histones adjacent to the transcription factor AP-1, NF-κB, and Pea3 binding sites of the MMP9 promoter, thereby suppressing MMP9 transcription, hence fixing MMP9 in the OFF mode. Conversely, when Smad3 is missing, this regulatory pathway is inactivated so that MMP9 is epigenetically turned ON. We postulate that these developmental epigenetic mechanisms by which Smad3 regulates MMP9 transcription cell autonomously may be important in modulating both emphysema and pulmonary fibrosis and that this could explain why both pathologies can appear within the same lung specimen.
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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.