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环状 RNA FTO 通过海绵吸附 miR-148a-3p 上调转化生长因子-α,从而调节高糖诱导的 ARPE-19 细胞损伤。

circFTO upregulates transforming growth factor-alpha through sponging miR-148a-3p to regulate high glucose-induced ARPE-19 cells injury.

机构信息

Department of Ophthalmology, The People's Hospital of Yubei District of Chongqing City, Chongqing, 401120, China.

Clinial Laboratory Chongqing, The People's Hospital of Yubei District of Chongqing City, Chongqing, 401120, China.

出版信息

Bioengineered. 2022 May;13(5):11489-11502. doi: 10.1080/21655979.2022.2067617.

Abstract

Diabetic retinopathy (DR) is one of the most common retinal microvascular diseases in diabetic patients. Therefore, elucidating the underlying molecular mechanism of DR is of great significance for its clinical treatment. This study explores the effects of the upregulated circFTO in DR patients in terms of cell apoptosis and viability. Several molecular assays are employed to explore these molecular mechanistic aspects, such as luciferase reporter, RNA pull-down, RT-qPCR, Western blot, and ELISA assays. miR-148a-3p is downregulated in DR patients. The expression of circFTO promoted ARPE-19 cells apoptosis and inhibited proliferation, reflecting the regulatory effect of circFTO/miR-148a-3p on retinal epithelial cells injury. In addition, the absence of circFTO could reduce ARPE-19 cells injury caused by HG by inhibiting oxidative stress and inflammation. Further, the investigations at the molecular level showed that circFTO could regulate the level of miR-148a-3p and TGFA . As the molecular sponge of miR-148a-3p, circFTO regulated cell viability and apoptosis and promoted the progression of DR through regulating the expression of TGFA. Together, this study provides new targets and markers for early diagnosis and therapy of DR.

摘要

糖尿病性视网膜病变 (DR) 是糖尿病患者最常见的视网膜微血管疾病之一。因此,阐明 DR 的潜在分子机制对于其临床治疗具有重要意义。本研究探讨了上调的 circFTO 在 DR 患者中对细胞凋亡和活力的影响。采用几种分子检测方法来探索这些分子机制方面,如荧光素酶报告、RNA 下拉、RT-qPCR、Western blot 和 ELISA 检测。在 DR 患者中,miR-148a-3p 表达下调。circFTO 的表达促进 ARPE-19 细胞凋亡并抑制增殖,反映了 circFTO/miR-148a-3p 对视网膜上皮细胞损伤的调节作用。此外,circFTO 的缺失可通过抑制氧化应激和炎症来减少 HG 引起的 ARPE-19 细胞损伤。进一步的分子水平研究表明,circFTO 可以调节 miR-148a-3p 和 TGFA 的水平。作为 miR-148a-3p 的分子海绵,circFTO 通过调节 TGFA 的表达来调节细胞活力和凋亡,从而促进 DR 的进展。总之,本研究为 DR 的早期诊断和治疗提供了新的靶点和标志物。

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