ArticleMolecular vision2015
Keratoconus in vitro and the key players of the TGF-β pathway.
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 46 papers, 2 of them syntheses that pooled it.
What it found
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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.
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, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Interleukin-1 and Transforming Growth Factor Beta: Commonly Opposing, but Sometimes Supporting, Master Regulators of the Corneal Wound Healing Response to Injury.Investigative ophthalmology & visual science · 2021Pooled it
- Systematically Displaying the Pathogenesis of KeratoconusFrontiers in medicine · 2021Pooled it
- Update on the Physiopathology of Keratoconus.Medical sciences (Basel, Switzerland) · 2026Review
- In Vitro Assessment of Nintedanib in Keratoconus Corneal Stromal Microenvironment.Biomolecules · 2026Article
- Integrated multi-omics analysis combined with clinical validation reveals that HLA-DRB5 and ODAPH are causal risk genes for keratoconus.Scientific reports · 2026Article
- Tear cytokine profiles between children with allergic conjunctivitis at varying eye rubbing frequencies and keratoconus: A cross-sectional study.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026Article
- Tear MicroRNA-Based Molecular Signature for Keratoconus Stratification: A Cross-Cohort Integration Study.Bioinformatics and biology insights · 2026Article
- Proteomic Analysis Provides Insights Into PPIP5K2 Function and Its Impact on Corneal Energy Metabolism.Investigative ophthalmology & visual science · 2025Article
- Exploring biomarkers for keratoconus: current insights and future directions.Molecular biology reports · 2025Review
- Regulation of corneal stromal cell behavior by modulating curvature using a hydraulically-controlled organ chip array.Nature communications · 2025Article
- Analysis of progranulin concentration in corneal epithelium and tears as a possible biomarker in the clinical diagnosis and progression of keratoconus.International ophthalmology · 2025Article
- Mechanical Strain of Corneal Epithelium Influences the Expression of Genes Implicated in Keratoconus.Investigative ophthalmology & visual science · 2025Article
- Article
- Review
- Identification of hub genes and molecular pathways in keratoconus by integrating bioinformatics and literature mining at the RNA level.International ophthalmology · 2024Article
- Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea.International journal of molecular sciences · 2024Article
- Ten-year incidence of keratoconus in relation to sex, age, and thyroid gland dysfunction: a nationwide population-based cohort study (2009-2018).Annals of translational medicine · 2024Article
- Exploration of Perturbed Liver Fibrosis-Related Factors and Collagen Type I in Animal Model of Non-Alcoholic Fatty Liver Disease.Applied biochemistry and biotechnology · 2024Article
- SMAD4-Dependent Signaling Pathway Involves in the Pathogenesis of TGFBR2-Related CE-like Phenotype.Cells · 2024Article
- Lack of Elevated Expression of TGFβ3 Contributes to the Delay of Epithelial Wound Healing in Diabetic Corneas.Investigative ophthalmology & visual science · 2024Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
purposeKeratoconus (KC) is a corneal thinning disease of unknown etiology whose pathophysiology is correlated with the presence of a thin corneal stroma and altered extracellular matrix (ECM). Transforming growth factor-β (TGF-β) signaling is a key regulator of ECM secretion and assembly in multiple tissues, including the anterior segment of the eye, and it has been linked to KC. We have previously shown that human keratoconus cells (HKCs) have a myofibroblast phenotype and altered ECM assembly compared to normal human corneal fibroblasts (HCFs). Moreover, TGF-β3 treatment promotes assembly of a more normal stromal ECM and modulates the fibrotic phenotype in HKCs. Herein, we identify alterations in TGF-β signaling that contribute to the observed fibrotic phenotype in HKCs.
methodsHCFs and HKCs were stimulated with TGF-β1, TGF-β2, or TGF-β3 isoforms (0.1 ng/mL) in the presence of a stable vitamin C derivative (0.5 mM) for 4 weeks. All samples were examined using RT-PCR and western blotting to quantify changes in the expressions of key TGF-β signaling molecules between HCFs and HKCs.
resultsWe found a significant downregulation in the SMAD6 and SMAD7 expressions by HKCs when compared to HCFs (p≤0.05). Moreover, stimulation of HKCs with any of the three TGF-β isoforms did not significantly alter the expressions of SMAD6 or SMAD7. HCFs also showed an upregulation in TGF-βRI, TGF-βRII, and TGF-βRIII following TGF-β3 treatment, whereas HKCs showed a significant two-fold downregulation.
conclusionsOverall, our data shows the decreased expressions of the regulatory SMADs SMAD6 and SMAD7 by HKCs contribute to the pathological ECM structure observed in KC, and TGF-β3 may attenuate this mechanism by downregulating the expression of the key profibrotic receptor, TGF-βRII. Our study suggests a significant role of altered regulation of TGF-β signaling in KC progression and that it may enable novel therapeutic developments targeting TGF-β receptor regulation.
Indexed as
Identifiers
26015770PMC4443584W2283583144What 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.