ArticleMolecular vision2015
Role of 5'TG3'-interacting factors (TGIFs) in Vorinostat (HDAC inhibitor)-mediated Corneal Fibrosis Inhibition.
Article in Molecular vision, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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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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Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
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- Epigenetic Reprogramming Via Sodium Butyrate Induces Corneal Myofibroblast Dedifferentiation In Vitro and Inhibits Fibrosis In Vivo.Investigative ophthalmology & visual science · 2025Article
- PI3K signaling and lysyl oxidase is critical to corneal stroma fibrosis following mustard gas injury.Experimental eye research · 2025Article
- Role of epigenetics in corneal health and disease.Progress in retinal and eye research · 2025Review
- Mustard Gas Exposure Actuates SMAD2/3 Signaling to Promote Myofibroblast Generation in the Cornea.Cells · 2023Article
- MiR-424/TGIF2-Mediated Pro-Fibrogenic Responses in Oral Submucous Fibrosis.International journal of molecular sciences · 2023Article
- Review
- Corneal stromal repair and regeneration.Progress in retinal and eye research · 2022Review
- Evaluation of CRISPR/Cas9 mediated TGIF gene editing to inhibit corneal fibrosis in vitro.Experimental eye research · 2022Article
- CtBP2 interacts with TGIF to promote the progression of esophageal squamous cell cancer through the Wnt/β‑catenin pathway.Oncology reports · 2022Article
- Pathological matrix stiffness promotes cardiac fibroblast differentiation through the POU2F1 signaling pathway.Science China. Life sciences · 2021Article
- Corneal stromal wound healing: Major regulators and therapeutic targets.The ocular surface · 2021Review
- A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study.Translational vision science & technology · 2020Article
- Role ofMolecular vision · 2020Article
- Corneal injury: Clinical and molecular aspects.Experimental eye research · 2019Review
- Altering equine corneal fibroblast differentiation through Smad gene transfer.Veterinary ophthalmology · 2018Article
- Article
- Development of a novel ex vivo equine corneal model.Veterinary ophthalmology · 2017Article
- Article
- Epigenetic Modification Prevents Excessive Wound Healing and Scar Formation After Glaucoma Filtration Surgery.Investigative ophthalmology & visual science · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeWe have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5'TG3'-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat.
methodsHuman corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were exposed to vorinostat (2.5 µM) to test its effect on TGIF mRNA and protein levels using qPCR and immunoblotting. Myofibroblast formation was induced with TGFβ1 (5 ng/ml) treatment under serum-free conditions. The changes in fibrosis parameters were quantified by measuring fibrosis marker α-smooth muscle actin (αSMA) mRNA and protein levels with qPCR, immunostaining, and immunoblotting. Smad2/3/4 and TGIF knockdowns were performed using pre-validated RNAi/siRNAs and a commercially available transfection reagent.
resultsHuman corneal fibroblasts showed the expression of TGIF1 and TGIF2. Vorinostat (2.5 µM) caused a 2.8-3.3-fold increase in TGIF1 and TGIF2 mRNA levels and a 1.4-1.8-fold increase in TGIF1 and TGIF2 protein levels. Vorinostat treatment also caused a significant increase in acetylhistone H3 and acetylhistone H4. Vorinostat-induced increases in TGIF1 and TGIF2 were accompanied by a concurrent decrease in corneal fibrosis, as indicated by a decrease in αSMA mRNA by 83±7.7% and protein levels by 97±5%. The RNAi-mediated knockdown of Smad2, Smad3, and Smad4 markedly attenuated TGFβ1-evoked transdifferentiation of fibroblasts to myofibroblasts. The siRNA-mediated knockdown of TGIF1 and TGIF2 neutralized vorinostat-evoked decreases in αSMA mRNA by 31%-45% and protein levels by 12%-23%.
conclusionsHuman corneal fibroblasts demonstrate the expression of TGIF1 and TGIF2 transcription factors. These transcriptional repressors are critical, at least partially, in mediating the antifibrotic effect of vorinostat in the cornea.
Indexed as
Identifiers
26330748PMC4551282W1954550383What 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.