ArticleAmerican journal of physiology. Cell physiology2015
TGF-β1 epigenetically modifies Thy-1 expression in primary lung fibroblasts.
Article in American journal of physiology. Cell physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 70 citations in OpenAlex.
- TGF-β1 Induced Methylation to Regulate SOCS3 Expression in Abnormal Activation of Vocal Fold Fibroblasts.World journal of otorhinolaryngology - head and neck surgery · 2026Article
- Treatment of pulmonary fibrosis: From disease mechanisms to future novel therapies (Review).International journal of molecular medicine · 2026Review
- Exploring the role of epigenetics in the processes related to the development of endometrosis in the mare.The Journal of reproduction and development · 2026Review
- HOXA2 exerts anti-renal fibrosis effects through reducing endoplasmic reticulum stress via the upregulation of SIRT1.Communications biology · 2025Article
- Significance of Epigenetic Alteration in Cancer-Associated Fibroblasts on the Development of Carcinoma.International journal of molecular sciences · 2025Review
- Integration of spatial protein imaging and transcriptomics in the human kidney tracks the regenerative potential of proximal tubules.Science advances · 2025Article
- Mechanisms and Therapeutic Potential of Myofibroblast Transformation in Pulmonary Fibrosis.Journal of respiratory biology and translational medicine · 2025Article
- Association between single nucleotide polymorphisms, TGF-β1 promoter methylation, and polycystic ovary syndrome.BMC pregnancy and childbirth · 2024Article
- Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Advances in cellular senescence in idiopathic pulmonary fibrosis (Review).Experimental and therapeutic medicine · 2023Review
- 5-Aza-2'-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts.Animals : an open access journal from MDPI · 2023Article
- Epigenetics Approaches toward Precision Medicine for Idiopathic Pulmonary Fibrosis: Focus on DNA Methylation.Biomedicines · 2023Review
- The Genetic and Epigenetic Footprint in Idiopathic Pulmonary Fibrosis and Familial Pulmonary Fibrosis: A State-of-the-Art Review.Diagnostics (Basel, Switzerland) · 2022Review
- DNA methylation in pulmonary fibrosis and lung cancer.Expert review of respiratory medicine · 2022Review
- Thy-1-Integrin Interactions inFrontiers in cell and developmental biology · 2022Review
- Epigenetic Changes and Functions in Pneumoconiosis.Oxidative medicine and cellular longevity · 2022Review
- TGF‑β1: Gentlemanly orchestrator in idiopathic pulmonary fibrosis (Review).International journal of molecular medicine · 2021Review
- More than a Genetic Code: Epigenetics of Lung Fibrosis.Molecular diagnosis & therapy · 2020Review
- Sirtuin 6 deficiency transcriptionally up-regulates TGF-β signaling and induces fibrosis in mice.The Journal of biological chemistry · 2020Article
- Stomatin plays a suppressor role in non-small cell lung cancer metastasis.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2019Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Idiopathic pulmonary fibrosis is a progressive lung disease that increases in incidence with age. We identified a profibrotic lung phenotype in aging mice characterized by an increase in the number of fibroblasts lacking the expression of thymocyte differentiation antigen 1 (Thy-1) and an increase in transforming growth factor (TGF)-β1 expression. It has been shown that Thy-1 expression can be epigenetically modified. Lung fibroblasts (PLFs) were treated with TGF-β1 ± DNA methyltransferase (DNMT) inhibitor 5-aza-2'-deoxycytidine (5-AZA) and analyzed for Thy-1 gene and protein expression, DNMT protein expression, and activity. α-Smooth muscle actin (α-SMA) and collagen type 1 (Col1A1) gene and protein expression was assessed. PLFs were transfected with DNMT1 silencing RNA ± TGF-β1. TGF-β1 inhibited Thy-1 gene and protein expression in PLFs, and cotreatment with 5-AZA ameliorated this effect and appeared to inhibit DNMT1 activation. TGF-β1 induced Thy-1 promoter methylation as assessed by quantitative methyl PCR. Treatment with 5-AZA attenuated TGF-β1-induced Col1A1 gene and protein expression and α-SMA gene expression (but not α-SMA protein expression). Inhibiting DNMT1 with silencing RNA attenuated TGF-β1-induced DNMT activity and its downstream suppression of Thy-1 mRNA and protein expression as well as inhibited α-SMA mRNA and Col1A1 mRNA and protein expression, and showed a decreased trend in Thy-1 promoter methylation. Immunofluorescence for α-SMA suggested that 5-AZA inhibited stress fiber formation. These findings suggest that TGF-β1 epigenetically regulates lung fibroblast phenotype through methylation of the Thy-1 promoter. Targeted inhibition of DNMT in the right clinical context might prevent fibroblast to myofibroblast transdifferentiation and collagen deposition, which in turn could prevent fibrogenesis in the lung and other organs.
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