Glaucoma filtration surgery (GFS) is a classic surgical method used to treat glaucoma, the second leading cause of blindness. Scar formation caused by excessive Tenon's capsule fibroblast activation leads to surgical failure. However, the mechanism underlying this activation is largely unknown. In this study, we first isolated primary human Tenon's capsule fibroblasts (HTFs) and found that TGF-β promoted the viability, proliferation and extracellular matrix (ECM) deposition of HTFs. Then, we showed that TGF-β promoted the expression of H19 in HTFs and that suppression of H19 inhibited the effect of TGF-β on HTFs. Furthermore, we revealed that H19 exerted its effects by interacting with miR-200a in TGF-β-treated HTFs. Additionally, we showed that β-catenin was a target of miR-200a in TGF-β-treated HTFs. We also demonstrated that H19 acted by modulating the H19/miR-200a/β-catenin regulatory axis in TGF-β-treated HTFs. Ultimately, we found that the components of the H19/miR-200a/β-catenin regulatory axis were aberrantly expressed in a rat model of GFS. Our results show that H19 indeed acts by modulating β-catenin expression via miR-200a in TGF-β-treated HTFs, thus providing a novel rationale for the development of H19-based strategies to attenuate scar formation after GFS.

中文翻译：

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长非编码RNA H19在TGF-β1诱导的Tenon's胶囊成纤维细胞增殖和细胞外基质沉积中的作用。

青光眼滤过手术（GFS）是用于治疗青光眼（失明的第二大原因）的经典手术方法。Tenon囊的成纤维细胞过度活化引起的疤痕形成会导致手术失败。但是，这种激活的基础机制在很大程度上尚不清楚。在这项研究中，我们首先分离了人类原发性人腱囊成纤维细胞（HTF），发现TGF-β促进了HTF的活力，增殖和细胞外基质（ECM）沉积。然后，我们表明TGF-β促进了HTF中H19的表达，并且抑制H19抑制了TGF-β对HTF的作用。此外，我们揭示了H19通过与TGF-β处理的HTF中的miR-200a相互作用发挥作用。此外，我们证明了在TGF-β处理的HTF中，β-catenin是miR-200a的靶标。我们还证明了H19通过调节TGF-β处理的HTF中的H19 / miR-200a /β-catenin调节轴起作用。最终，我们发现H19 / miR-200a /β-catenin调控轴的成分在GFS大鼠模型中异常表达。我们的结果表明，H19确实通过调节TGF-β处理的HTF中的miR-200a调节β-catenin的表达而起作用，从而为开发基于G19的G19减轻疤痕形成的策略提供了新的理论依据。