ArticlePloS one2017
Suppression of TGF-β pathway by pirfenidone decreases extracellular matrix deposition in ocular fibroblasts in vitro.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Fighting Bleb Fibrosis After Glaucoma Surgery: Updated Focus on Key Players and Novel Targets for Therapy.International journal of molecular sciences · 2025Pooled it
- A small-molecule TNIK inhibitor targets fibrosis in preclinical and clinical models.Nature biotechnology · 2025Trial
- Immunomodulation by collagen VI across fibrotic and tumor microenvironmental contexts.Histology and histopathology · 2026Review
- Targeting Inflammatory and Oxidative Pathways in Idiopathic Pulmonary Fibrosis: Synergistic Effects of Quercetin and Pirfenidone in Modulating Nrf2/PPAR-γ and TLR-4/NF-κB Pathways.Pharmacology research & perspectives · 2026Article
- Targeting macrophages in liver fibrosis.Frontiers in immunology · 2026Review
- Unveiling the Therapeutic Potential: A Peptide Drug Conjugate's Influence on Transcription and Translation in Ocular Fibrosis Modulation.ACS omega · 2025Article
- Article
- γ-Cyclodextrin hydrogel for the sustained release of josamycin for potential ocular application.Drug delivery · 2024Article
- Experimental glaucoma microstent implantation in two animal models and human donor eyes-anQuantitative imaging in medicine and surgery · 2024Article
- O-GlcNAc transferase regulates collagen deposition and fibrosis resolution in idiopathic pulmonary fibrosis.Frontiers in immunology · 2024Article
- Antioxidant, Antiinflammation, and Antifibrotic Activity of Ciplukan (Journal of inflammation research · 2024Article
- The protective effects of pirfenidone in preventing abdominal aortic aneurysm formation.Journal of biochemical and molecular toxicology · 2023Article
- Inhibition of TGF-β2-Induced Trabecular Meshwork Fibrosis by Pirfenidone.Translational vision science & technology · 2023Article
- Targeting transforming growth factor beta (TGF-β) using Pirfenidone, a potential repurposing therapeutic strategy in colorectal cancer.Scientific reports · 2023Article
- Can pirfenidone prevent tendon adhesions? An experimental study in rats.Joint diseases and related surgery · 2023Article
- Quantitative systems pharmacology of the eye: Tools and data for ocular QSP.CPT: pharmacometrics & systems pharmacology · 2023Review
- Review
- Losartan enhances the suppressive effect of pirfenidone on the bleomycin-induced epithelial-mesenchymal transition and oxidative stress in A549 cell line.Iranian journal of basic medical sciences · 2023Article
- Prevention of Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice by Bilobalide.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- The NLRP3 Activation in Infiltrating Macrophages Contributes to Corneal Fibrosis by Inducing TGF-β1 Expression in the Corneal Epithelium.Investigative ophthalmology & visual science · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In glaucoma surgery, fibrotic processes occur, leading to impairment of liquid outflow. Activated fibroblasts are responsible for postoperative scarring. The transforming growth factor-β (TGF-β) pathway plays a key role in fibroblast function, differentiation and proliferation. The aim of this study was the characterization of the fibrotic potential of two subtypes of primary human ocular fibroblasts and the attempt to inhibit fibrotic processes specifically, without impairing cell viability. For fibrosis inhibition we focused on the small molecule pirfenidone, which has been shown to prevent pulmonary fibrosis by the decrease of the expression of TGF-β1, TGF-β2 and TGF-β3 cytokines. For in vitro examinations, isolated human primary fibroblasts from Tenon capsule and human intraconal orbital fat tissues were used. These fibroblast subpopulations were analyzed in terms of the expression of matrix components responsible for postoperative scarring. We concentrated on the expression of collagen I, III, VI and fibronectin. Additionally, we analyzed the expression of α-smooth muscle actin, which serves as a marker for fibrosis and indicates transformation of fibroblasts into myofibroblasts. Gene expression was analyzed by rtPCR and synthesized proteins were examined by immunofluorescence and Western blot methods. Proliferation of fibroblasts under different culture conditions was assessed using BrdU assay. TGF-β1 induced a significant increase of cell proliferation in both cell types. Also the expression of some fibrotic markers was elevated. In contrast, pirfenidone decreased cell proliferation and matrix synthesis in both fibroblast subpopulations. Pirfenidone slightly attenuated TGF-β1 induced expression of fibronectin and α-smooth muscle actin in fibroblast cultures, without impairing cell viability. To summarize, manipulation of the TGF-β signaling pathway by pirfenidone represents a specific antifibrotic approach with no toxic side effects in two human orbital fibroblast subtypes. We presume that pirfenidone is a promising candidate for the treatment of fibrosis following glaucoma surgery.
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