Current eye research · 2026
LncRNA H19 Promotes H2O2-Induced Human Trabecular Meshwork Cell Injury and Extracellular Matrix Production by Regulating the miR-20a-5p/Smad4 Axis.
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Wang Bin, Li Xudong
Аннотация
PURPOSE: Primary open-angle glaucoma is characterized by trabecular meshwork cell injury and excessive extracellular matrix deposition. Given the established involvement of long non-coding RNAs in primary open-angle glaucoma pathogenesis, this study investigates the role and mechanism of long non-coding RNA H19 in mediating trabecular meshwork cell dysfunction and extracellular matrix production.
METHODS: Hydrogen peroxide-treated human trabecular meshwork cells were used to establish in vitro primary open-angle glaucoma models. Cell viability and apoptosis were assessed via cell counting kit-8 and flow cytometry. Gene/protein expression of H19, Smad4, and extracellular matrix components (fibronectin, collagen I, and laminin) was evaluated by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. Subcellular H19 localization was determined by nuclear-cytoplasmic fractionation. The H19-miR-20a-5p-Smad4 regulatory axis was validated through luciferase reporter assays and rescue experiments across three characterized human trabecular meshwork cell strains.
RESULTS: Hydrogen peroxide exposure induced concentration-dependent human trabecular meshwork cell injury and significantly upregulated H19 and Smad4 expression (p < 0.001). H19 knockdown attenuated oxidative damage, restoring viability (p < 0.001), reducing apoptosis (p < 0.001), and suppressing extracellular matrix deposition (p < 0.001). Mechanistically, H19 functioned as a competing endogenous RNA by binding miR-20a-5p, which targeted Smad4. Smad4 overexpression or miR-20a-5p inhibition abrogated H19 deficiency-mediated protection. Notably, H19 knockdown also reduced transforming growth factor-beta/Smad signaling (p < 0.001) while enhancing nuclear factor erythroid 2-related factor 2/heme oxygenase-1 antioxidant responses (p < 0.001).
CONCLUSION: Long non-coding RNA H19 facilitates hydrogen peroxide-induced human trabecular meshwork cell injury and extracellular matrix deposition primarily by orchestrating the miR-20a-5p/Smad4 axis, with additional modulation of transforming growth factor-beta/Smad and nuclear factor erythroid 2-related factor 2 pathways.
METHODS: Hydrogen peroxide-treated human trabecular meshwork cells were used to establish in vitro primary open-angle glaucoma models. Cell viability and apoptosis were assessed via cell counting kit-8 and flow cytometry. Gene/protein expression of H19, Smad4, and extracellular matrix components (fibronectin, collagen I, and laminin) was evaluated by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. Subcellular H19 localization was determined by nuclear-cytoplasmic fractionation. The H19-miR-20a-5p-Smad4 regulatory axis was validated through luciferase reporter assays and rescue experiments across three characterized human trabecular meshwork cell strains.
RESULTS: Hydrogen peroxide exposure induced concentration-dependent human trabecular meshwork cell injury and significantly upregulated H19 and Smad4 expression (p < 0.001). H19 knockdown attenuated oxidative damage, restoring viability (p < 0.001), reducing apoptosis (p < 0.001), and suppressing extracellular matrix deposition (p < 0.001). Mechanistically, H19 functioned as a competing endogenous RNA by binding miR-20a-5p, which targeted Smad4. Smad4 overexpression or miR-20a-5p inhibition abrogated H19 deficiency-mediated protection. Notably, H19 knockdown also reduced transforming growth factor-beta/Smad signaling (p < 0.001) while enhancing nuclear factor erythroid 2-related factor 2/heme oxygenase-1 antioxidant responses (p < 0.001).
CONCLUSION: Long non-coding RNA H19 facilitates hydrogen peroxide-induced human trabecular meshwork cell injury and extracellular matrix deposition primarily by orchestrating the miR-20a-5p/Smad4 axis, with additional modulation of transforming growth factor-beta/Smad and nuclear factor erythroid 2-related factor 2 pathways.