Knockdown of HOTAIR Alleviates High Glucose-Induced Apoptosis and Inflammation in Retinal Pigment Epithelial Cells.

IF 3.1 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yanping Wu, Zenghui Liang, Kun Li, Junli Feng
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Abstract

Diabetic retinopathy (DR) is one of the most common microvascular complications in diabetes. Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) played critical regulatory roles in DR. However, the role of lncRNA HOX Transcript Antisense Intergenic RNA (HOTAIR) in the high glucose (HG)-induced human retinal pigment epithelial (RPE) cell injury remains unclear. Herein, we found the expression of HOTAIR was increased in the retina of DR rats and HG-induced ARPE-19 cells. Knockdown of HOTAIR improved viability, inhibited apoptosis, increased Bcl-2 protein levels, and decreased Bax and cleaved caspase 3 protein levels in HG-treated ARPE-19 cells. Moreover, enzyme-linked immunosorbent assay showed that HOTAIR silencing reduced interleukin 6 and tumor necrosis factor-α release of ARPE-19 cells under HG conditions. Mechanistically, luciferase reporter assay and RNA immunoprecipitation assay validated that HOTAIR could directly sponge miR-326 to upregulate transcription factor 4 (TCF4) expression. Furthermore, rescue experiments confirmed that HOTAIR promoted apoptosis and inflammation of HG-treated ARPE-19 cells by the miR-326/TCF4 axis. In summary, HOTAIR enhanced HG-induced retinal pigment epithelial cell injury by promoting apoptosis and inflammation, shedding light on the importance of HOTAIR as a novel potential target for DR treatment.

敲除 HOTAIR 可缓解高血糖诱导的视网膜色素上皮细胞凋亡和炎症。
糖尿病视网膜病变(DR)是糖尿病最常见的微血管并发症之一。越来越多的证据表明,长非编码 RNA(lncRNA)在 DR 中发挥着关键的调控作用。然而,lncRNA HOX Transcript Antisense Intergenic RNA(HOTAIR)在高糖(HG)诱导的人视网膜色素上皮(RPE)细胞损伤中的作用仍不清楚。在本文中,我们发现 HOTAIR 在 DR 大鼠视网膜和 HG 诱导的 ARPE-19 细胞中表达增加。在 HG 处理的 ARPE-19 细胞中,敲除 HOTAIR 能提高细胞活力、抑制细胞凋亡、提高 Bcl-2 蛋白水平、降低 Bax 和裂解的 caspase 3 蛋白水平。此外,酶联免疫吸附试验表明,在 HG 条件下,沉默 HOTAIR 可减少 ARPE-19 细胞白细胞介素 6 和肿瘤坏死因子-α 的释放。从机理上讲,荧光素酶报告实验和 RNA 免疫沉淀实验验证了 HOTAIR 可直接海绵状表达 miR-326,从而上调转录因子 4(TCF4)的表达。此外,拯救实验证实,HOTAIR 通过 miR-326/TCF4 轴促进了 HG 处理的 ARPE-19 细胞的凋亡和炎症反应。总之,HOTAIR通过促进细胞凋亡和炎症反应增强了HG诱导的视网膜色素上皮细胞损伤,从而揭示了HOTAIR作为DR治疗潜在新靶点的重要性。
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来源期刊
Applied Biochemistry and Biotechnology
Applied Biochemistry and Biotechnology 工程技术-生化与分子生物学
CiteScore
5.70
自引率
6.70%
发文量
460
审稿时长
5.3 months
期刊介绍: This journal is devoted to publishing the highest quality innovative papers in the fields of biochemistry and biotechnology. The typical focus of the journal is to report applications of novel scientific and technological breakthroughs, as well as technological subjects that are still in the proof-of-concept stage. Applied Biochemistry and Biotechnology provides a forum for case studies and practical concepts of biotechnology, utilization, including controls, statistical data analysis, problem descriptions unique to a particular application, and bioprocess economic analyses. The journal publishes reviews deemed of interest to readers, as well as book reviews, meeting and symposia notices, and news items relating to biotechnology in both the industrial and academic communities. In addition, Applied Biochemistry and Biotechnology often publishes lists of patents and publications of special interest to readers.
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