Abstract

Background

Recent studies have provided strong evidence that lncRNAs play a functional regulatory role in diabetic retinopathy (DR). The purpose of this study was to investigate the effect of long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) in DR.

Methods

A DR mouse model was established by intraperitoneal injection of streptozotocin (STZ), and then the mouse retinal Müller cells (mMCs) were isolated from retina tissues of mice. Human retinal Müller cell line (HMCs) and mMCs and were treated with high glucose (HG) to simulate an in vitro DR model. XIST expression was detected by qRT-PCR. Next, XIST overexpression was performed in mMCs and HMCs to examine its effect on the activation of Müller cells and production of pro-inflammatory cytokines. Subsequently, the interaction between XIST and SIRT1 was verified, and the ubiquitination level of SIRT1 as well as the stability of SIRT1 protein were assessed.

Results

XIST was down-regulated in retinal tissues of DR mice and HG-induced HMCs. Overexpression of XIST inhibited HG-induced activation of mMCs and HMCs, and reduced the production of pro-inflammatory cytokines. XIST promoted SIRT1 expression via interacting with SIRT1 and inhibiting the ubiquitination of SIRT1. Furthermore, SIRT1 silencing partly abrogated the effect of XIST overexpression on the activation of mMCs and HMCs as well as the production of pro-inflammatory cytokines induced by HG.

Conclusion

We concluded that XIST restrained the activation of Müller cells and the production of pro-inflammatory cytokines via stabilizing SIRT1.

中文翻译：

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LncRNA XIST 通过稳定 SIRT1 抑制糖尿病视网膜病变中 Müller 细胞的活化和炎症

摘要

背景

最近的研究提供了强有力的证据表明 lncRNA 在糖尿病视网膜病变 (DR) 中发挥功能调节作用。本研究的目的是研究长链非编码 RNA (lncRNA) X 非活性特异性转录本 (XIST) 在 DR 中的作用。

方法

通过腹腔注射链脲佐菌素（STZ）建立DR小鼠模型，然后从小鼠视网膜组织中分离出小鼠视网膜Müller细胞（mmCs）。人视网膜 Müller 细胞系 (HMC) 和 mmC，并用高葡萄糖 (HG) 处理以模拟体外DR 模型。通过 qRT-PCR 检测 XIST 表达。接下来，在 mMCs 和 HMCs 中进行 XIST 过表达，以检查其对 Müller 细胞活化和促炎细胞因子产生的影响。随后，验证了XIST与SIRT1的相互作用，并评估了SIRT1的泛素化水平以及SIRT1蛋白的稳定性。

结果

XIST 在 DR 小鼠和 HG 诱导的 HMC 的视网膜组织中下调。XIST 的过表达抑制了 HG 诱导的 mMCs 和 HMCs 的活化，并减少了促炎细胞因子的产生。XIST通过与 SIRT1 相互作用并抑制 SIRT1 的泛素化来促进 SIRT1 的表达。此外，SIRT1 沉默部分消除了 XIST 过表达对 mMC 和 HMC 活化以及 HG 诱导的促炎细胞因子产生的影响。

结论

我们得出结论，XIST通过稳定 SIRT1抑制了 Müller 细胞的活化和促炎细胞因子的产生。