ArticleClinical science (London, England : 1979)2016
Epigenetic regulation of cyclooxygenase-2 by methylation of c8orf4 in pulmonary fibrosis.
Article in Clinical science (London, England : 1979), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- Unfolding the pathogenesis of scleroderma through genomics and epigenomics.Journal of autoimmunity · 2017Pooled it
- TGF-β-induced epigenetic deregulation of SOCS3 facilitates STAT3 signaling to promote fibrosis.The Journal of clinical investigation · 2020Trial
- Expanding role of cell-free DNA for the early diagnosis and monitoring of pulmonary diseases.Chinese medical journal · 2026Review
- Plant-Derived Agents and Systemic Sclerosis: A Systematic Review of Therapeutic Potential and Molecular Mechanisms.Current issues in molecular biology · 2026Review
- Mechanistic basis for the antifibrotic actions of cAMP-based therapies.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Decoding Dysregulation of DNA Methylation in Epigenetics of Idiopathic Pulmonary Fibrosis.Canadian respiratory journal · 2026Review
- Epigenetic regulatory mechanisms and translational applications in idiopathic pulmonary fibrosis.American journal of clinical and experimental immunology · 2026Review
- Prostaglandin EEXCLI journal · 2025Review
- DNA methylation in human diseases.Heliyon · 2024Review
- Different Levels of Autophagy Activity in Mesenchymal Stem Cells Are Involved in the Progression of Idiopathic Pulmonary Fibrosis.Stem cells international · 2024Review
- DNA methylation modification in Idiopathic pulmonary fibrosis.Frontiers in cell and developmental biology · 2024Review
- Genome-wide DNA methylation analysis of Astragalus and Danshen on the intervention of myofibroblast activation in idiopathic pulmonary fibrosis.BMC pulmonary medicine · 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
- Modulating epigenetic modifications for cancer therapy (Review).Oncology reports · 2023Review
- Transcriptomic profiles of age-related genes in female trachea and bronchus.Frontiers in genetics · 2023Article
- Bioinformatic identification and analysis of immune-related chromatin regulatory genes as potential biomarkers in idiopathic pulmonary fibrosis.Annals of translational medicine · 2022Article
- Therapeutic induction of Bcl2-associated athanogene 3-mediated autophagy in idiopathic pulmonary fibrosis.Clinical and translational medicine · 2022Article
- DNA methylation in pulmonary fibrosis and lung cancer.Expert review of respiratory medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblasts derived from the lungs of patients with idiopathic pulmonary fibrosis (IPF) and systemic sclerosis (SSc) produce low levels of prostaglandin (PG) E2, due to a limited capacity to up-regulate cyclooxygenase-2 (COX-2). This deficiency contributes functionally to the fibroproliferative state, however the mechanisms responsible are incompletely understood. In the present study, we examined whether the reduced level of COX-2 mRNA expression observed in fibrotic lung fibroblasts is regulated epigenetically. The DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5AZA) restored COX-2 mRNA expression by fibrotic lung fibroblasts dose dependently. Functionally, this resulted in normalization of fibroblast phenotype in terms of PGE2 production, collagen mRNA expression and sensitivity to apoptosis. COX-2 methylation assessed by bisulfite sequencing and methylation microarrays was not different in fibrotic fibroblasts compared with controls. However, further analysis of the methylation array data identified a transcriptional regulator, chromosome 8 open reading frame 4 (thyroid cancer protein 1, TC-1) (c8orf4), which is hypermethylated and down-regulated in fibrotic fibroblasts compared with controls. siRNA knockdown of c8orf4 in control fibroblasts down-regulated COX-2 and PGE2 production generating a phenotype similar to that observed in fibrotic lung fibroblasts. Chromatin immunoprecipitation demonstrated that c8orf4 regulates COX-2 expression in lung fibroblasts through binding of the proximal promoter. We conclude that the decreased capacity of fibrotic lung fibroblasts to up-regulate COX-2 expression and COX-2-derived PGE2 synthesis is due to an indirect epigenetic mechanism involving hypermethylation of the transcriptional regulator, c8orf4.
Indexed as
Identifiers
What OpenQuestion holds
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.