ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
Hypermethylation-mediated silencing of p14(ARF) in fibroblasts from idiopathic pulmonary fibrosis.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 94 citations in OpenAlex.
- Histone methyltransferase KMT2A promotes pulmonary fibrogenesis via targeting pro-fibrotic factor PU.1 in fibroblasts.Clinical and translational medicine · 2025Article
- Fibroblast and myofibroblast activation in normal tissue repair and fibrosis.Nature reviews. Molecular cell biology · 2024Review
- Cell Proliferation and Apoptosis-Key Players in the Lung Aging Process.International journal of molecular sciences · 2024Review
- Inhibitor of PD-1/PD-L1: a new approach may be beneficial for the treatment of idiopathic pulmonary fibrosis.Journal of translational medicine · 2024Review
- DNA methylation modification in Idiopathic pulmonary fibrosis.Frontiers in cell and developmental biology · 2024Review
- Single-nucleus chromatin accessibility identifies a critical role for TWIST1 in idiopathic pulmonary fibrosis myofibroblast activity.The European respiratory journal · 2023Article
- Towards a Unified Approach in Autoimmune Fibrotic Signalling Pathways.International journal of molecular sciences · 2023Review
- Hydrogel mechanics regulate fibroblast DNA methylation and chromatin condensation.Biomaterials science · 2023Article
- Review
- Epigenetics Approaches toward Precision Medicine for Idiopathic Pulmonary Fibrosis: Focus on DNA Methylation.Biomedicines · 2023Review
- Epigenetics as a versatile regulator of fibrosis.Journal of translational medicine · 2023Review
- Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.Cells · 2022Article
- DNA methylation in pulmonary fibrosis and lung cancer.Expert review of respiratory medicine · 2022Review
- Epigenetic Changes and Functions in Pneumoconiosis.Oxidative medicine and cellular longevity · 2022Review
- The role of PD-1/PD-L1 axis in idiopathic pulmonary fibrosis: Friend or foe?Frontiers in immunology · 2022Review
- Fibroblasts From Idiopathic Pulmonary Fibrosis Induce Apoptosis and Reduce the Migration Capacity of T Lymphocytes.Frontiers in immunology · 2022Article
- Transcriptomic and Epigenetic Profiling of Fibroblasts in Idiopathic Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2022Article
- Myofibroblast fate plasticity in tissue repair and fibrosis: Deactivation, apoptosis, senescence and reprogramming.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society · 2021Article
- Divergent Regulation of Alveolar Type 2 Cell and Fibroblast Apoptosis by Plasminogen Activator Inhibitor 1 in Lung Fibrosis.The American journal of pathology · 2021Article
- Targeting mechanosensitive MDM4 promotes lung fibrosis resolution in aged mice.The Journal of experimental medicine · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology. A conspicuous feature is the formation and persistence of fibroblastic/myofibroblastic foci throughout the lung parenchyma. Mechanisms remain unknown, but data indicate that fibroblasts acquire an antiapoptotic phenotype. We hypothesized that transcriptional silencing of proapoptotic genes may be implicated, and accordingly we evaluated the epigenetic regulation of p14(ARF). The expression of p14(ARF) was analyzed by RT-PCR in IPF (n = 8) and normal derived fibroblasts (n = 4) before and after treatment with 5-aza-2'-deoxycytidine (5-aza) and trichostatin A (TSA). p14(ARF) gene promoter methylation was determined by methylation-specific PCR (MS-PCR) and by DNA digestion with endonuclease McrBc, which cleaves 50% of methylated CpG. Apoptosis was evaluated by Annexin-V and nuclear staining. p14(ARF) expression was significantly decreased in four of the eight IPF fibroblasts lines, which was restored after 5-aza treatment. No changes were found with TSA. MS-PCR of bisulfite-treated genomic DNA showed a correlation between the reduced expression of p14(ARF) and the presence of hypermethylated promoter. No amplification was observed in the DNA treated with the McrBc enzyme, corroborating promoter hypermethylation. p14(ARF)-hypermethylated IPF fibroblasts were significantly more resistant to staurosporine-and S-nitrosoglutathione-induced apoptosis compared with normal and nonmethylated IPF fibroblasts (P < 0.01) and showed reduced levels of p53. Resistance to apoptosis was provoked in fibroblasts when p14(ARF) expression was inhibited by siRNA (P < 0.05). These findings demonstrate that many IPF fibroblasts have reduced expression of the proapoptotic p14(ARF) attributable to promoter hypermethylation and indicate that epigenetic mechanisms may underlie their resistance to apoptosis.
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