Department of Ophthalmology, Chonnam National University Medical School and Hospital, Gwangju 61469, Republic of Korea.
Department of Pharmacology, Chonnam National University Medical School, Hwasun 58128, Republic of Korea.
Int J Mol Sci. 2023 Jun 1;24(11):9625. doi: 10.3390/ijms24119625.
We aimed to investigate the effects of different concentrations of vascular endothelial growth factor (VEGF) on the extracellular matrix (ECM) and fibrotic proteins in human trabecular meshwork (TM) cells. We also explored how the Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ) signaling pathway modulates VEGF-induced fibrosis. We determined cross-linked actin network (CLAN) formation using TM cells. Changes in fibrotic and ECM protein expression were determined. High VEGF concentrations (10 and 30 ng/mL) increased TAZ and decreased p-TAZ/TAZ expression in TM cells. Western blotting and real-time PCR revealed no YAP expression changes. Fibrotic and ECM protein expression decreased at low VEGF concentrations (1 and 10 ρg/mL) and significantly increased at high VEGF concentrations (10 and 30 ng/mL). CLAN formation increased in TM cells treated with high VEGF concentrations. Moreover, TAZ inhibition by verteporfin (1 μM) rescued TM cells from high-VEGF-concentration-induced fibrosis. Low VEGF concentrations reduced fibrotic changes, whereas high VEGF concentrations accelerated fibrosis and CLAN formations in TM cells in a TAZ-dependent manner. These findings reflect the dose-dependent influences of VEGF on TM cells. Moreover, TAZ inhibition might be a therapeutic target for VEGF-induced TM dysfunction.
我们旨在研究不同浓度的血管内皮生长因子 (VEGF) 对人眼小梁网 (TM) 细胞细胞外基质 (ECM) 和纤维蛋白的影响。我们还探讨了 Yes 相关蛋白 (YAP)/含 PDZ 结合模体的转录共激活因子 (TAZ) 信号通路如何调节 VEGF 诱导的纤维化。我们使用 TM 细胞确定交联肌动蛋白网络 (CLAN) 的形成。测定纤维蛋白和 ECM 蛋白表达的变化。高浓度 VEGF（10 和 30ng/ml）增加了 TM 细胞中的 TAZ，并降低了 p-TAZ/TAZ 的表达。Western blot 和实时 PCR 显示 YAP 表达无变化。低浓度 VEGF（1 和 10μg/ml）时纤维蛋白和 ECM 蛋白表达减少，高浓度 VEGF（10 和 30ng/ml）时明显增加。高浓度 VEGF 处理的 TM 细胞中 CLAN 形成增加。此外，verteporfin（1μM）抑制 TAZ 可挽救高 VEGF 浓度诱导的 TM 细胞纤维化。低浓度 VEGF 减少了纤维变化，而高浓度 VEGF 以 TAZ 依赖的方式加速了 TM 细胞的纤维化和 CLAN 形成。这些发现反映了 VEGF 对 TM 细胞的剂量依赖性影响。此外，TAZ 抑制可能是治疗 VEGF 诱导的 TM 功能障碍的靶点。
