Liu Bei-Yan, Li Lin, Bai Li-Wei, Xu Chang-Shui
Department of Endocrinology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China.
Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China.
Front Mol Biosci. 2021 Apr 28;8:655157. doi: 10.3389/fmolb.2021.655157. eCollection 2021.
Diabetic peripheral neuropathy (DPN) is a prevalent diabetes mellitus (Feldman et al., 2017) complication and the primary reason for amputation. Meanwhile, long non-coding RNAs (lncRNAs) are a type of regulatory non-coding RNAs (ncRNAs) that broadly participate in DPN development. However, the correlation of lncRNA X-inactive specific transcript (XIST) with DPN remains unclear. In this study, we were interested in the role of XIST in the modulation of DPN progression. Significantly, our data showed that the expression of and sirtuin1 (SIRT1) was inhibited, and the expression of microRNA-30d-5p () was enhanced in the trigeminal sensory neurons of the diabetic mice compared with the normal mice. The levels of LC3II and Beclin-1 were inhibited in the diabetic mice. The treatment of high glucose (HG) reduced the XIST expression in Schwann cells. The apoptosis of Schwann cells was enhanced in the HG-treated cells, but the overexpression of could block the effect in the cells. Moreover, the levels of LC3II and Beclin-1 were reduced in the HG-treated Schwann cells, while the overexpression of was able to reverse this effect. The HG treatment promoted the production of oxidative stress, while the overexpression could attenuate this result in the Schwann cells. Mechanically, was able to sponge and -targeted SIRT1 in the Schwann cells. inhibited autophagy and promoted oxidative stress in the HG-treated Schwann cells, and SIRT1 presented a reversed effect. mimic or SIRT1 depletion could reverse overexpression-mediated apoptosis and autophagy of the Schwann cells. Thus, we concluded that attenuated DPN by inducing autophagy through /SIRT1 axis. XIST and may be applied as the potential targets for DPN therapy.
糖尿病周围神经病变（DPN）是一种常见的糖尿病并发症（费尔德曼等人，2017年），也是截肢的主要原因。同时，长链非编码RNA（lncRNAs）是一类调控性非编码RNA（ncRNAs），广泛参与DPN的发展。然而，lncRNA X染色体失活特异性转录本（XIST）与DPN的相关性仍不清楚。在本研究中，我们关注XIST在调节DPN进展中的作用。值得注意的是，我们的数据显示，与正常小鼠相比，糖尿病小鼠三叉神经感觉神经元中[此处原文缺失部分基因名称]和沉默调节蛋白1（SIRT1）的表达受到抑制，而微小RNA-30d-5p（[此处原文缺失部分基因名称]）的表达增强。糖尿病小鼠中LC3II和Beclin-1的水平受到抑制。高糖（HG）处理降低了雪旺细胞中XIST的表达。HG处理的细胞中雪旺细胞的凋亡增强，但[此处原文缺失部分基因名称]的过表达可阻断细胞中的这种作用。此外，HG处理的雪旺细胞中LC3II和Beclin-1的水平降低，而[此处原文缺失部分基因名称]的过表达能够逆转这种作用。HG处理促进了氧化应激的产生，而[此处原文缺失部分基因名称]的过表达可减轻雪旺细胞中的这一结果。从机制上讲，[此处原文缺失部分基因名称]能够在雪旺细胞中吸附[此处原文缺失部分基因名称]并靶向SIRT1。[此处原文缺失部分基因名称]在HG处理的雪旺细胞中抑制自噬并促进氧化应激，而SIRT1则呈现相反的作用。[此处原文缺失部分基因名称]模拟物或SIRT1缺失可逆转[此处原文缺失部分基因名称]过表达介导的雪旺细胞凋亡和自噬。因此，我们得出结论，[此处原文缺失部分基因名称]通过[此处原文缺失部分基因名称]/SIRT1轴诱导自噬来减轻DPN。XIST和[此处原文缺失部分基因名称]可能作为DPN治疗的潜在靶点。
