ArticleJournal of biomedical science2019
Glucosamine impedes transforming growth factor β1-mediated corneal fibroblast differentiation by targeting Krüppel-like factor 4.
Article in Journal of biomedical science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 11 citations in OpenAlex.
- Identification of genetic variants in five chinese families with keratoconus: Pathogenicity analysis and characteristics of parental corneal topography.Frontiers in genetics · 2022Pooled it
- TGF-β1/SMAD signaling downregulates KLF4 expression via direct transcriptional suppression and FAT10-mediated proteasomal degradation in hepatocellular carcinoma.Cell & bioscience · 2026Article
- Glucosamine mitigates hyperglycemic-induced oxidative stress via the SIRT1 pathway in human corneal epithelial cells.Scientific reports · 2025Article
- The cell-fate decision of dental follicle stem cells (DFSCs) with porcine corneal extracellular matrix (ECM).Journal of dental sciences · 2025Article
- FTO-mediated m6A demethylation of KLF4 promotes the proliferation and collagen deposition of keloid fibroblasts.Toxicology research · 2025Article
- Non-coding RNA in cartilage regeneration: regulatory mechanism and therapeutic strategies.Frontiers in bioengineering and biotechnology · 2025Review
- The Long Noncoding RNADNA and cell biology · 2022Article
- KLF4 Alleviates Hypertrophic Scar Fibrosis by Directly Activating BMP4 Transcription.International journal of biological sciences · 2022Article
- Glucosamine inhibits extracellular matrix accumulation in experimental diabetic nephropathy.Frontiers in nutrition · 2022Article
- Long Non-Coding RNA (lncRNA) Small Nucleolar RNA Host Gene 15 (SNHG15) Alleviates Osteoarthritis Progression by Regulation of Extracellular Matrix Homeostasis.Medical science monitor : international medical journal of experimental and clinical research · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTransforming growth factor (TGF) family members play important roles in the regulation of corneal integrity, and the pathogenesis of corneal fibrosis. Currently, there are no effective agents targeting TGF-β signaling to diminish corneal fibrosis. Glucosamine (GlcN), which is widely used in the treatment of osteoarthritis, abrogates the morphologic effects of TGF-β2 on retinal pigmented epithelial cells in a mouse disease model. Here, we sought to determine whether GlcN would exert beneficial effects against TGF-β1-induced corneal fibrosis.
methodsIn human corneal fibroblasts (HCFs) treated with GlcN, the expression of Krüppel-like factor 4 (KLF4) and its downstream signaling effects were determined in the presence and absence of TGF-β1 using immunoblot analysis. We further explored GlcN inhibition of fibroblast-to-myofibroblast differentiation via KLF4 siRNA. The effect of cycloheximide on KLF4 protein levels with or without GlcN administration was assessed to determine whether GlcN affects the stability of the KLF4 protein.
resultsIn HCFs, GlcN induced the expression of KLF4, which regulated the maturation and maintenance of the ocular surface. GlcN partially suppressed the TGF-β1-induced expression of alpha-smooth muscle actin (α-SMA) and reduced the collagen contraction capacity in HCFs, suggesting a decrease in fibroblast-to-myofibroblast differentiation. This effect appeared to be mediated through suppression of Smad2 phosphorylation and ERK-dependent signaling. The levels of KLF4 mRNA were increased by GlcN and decreased by TGF-β1 and the TGF-β1-induced α-SMA mRNA expression was upregulated when the KLF4 gene was silenced. GlcN also appeared to stabilize the KLF4 protein, reducing its turnover in corneal fibroblasts.
conclusionThese findings shed light on a novel mechanism by which GlcN suppresses TGF-β1-induced fibroblast-to-myofibroblast differentiation through the upregulation of KLF4 expression. Current strategies for treating corneal fibrosis were not effective. Elevating KLF4 levels through the use of GlcN might provide an effective alternative to alleviate the development and progression of corneal fibrosis.
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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.