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高表达 microRNA-20b-3p 和低表达硫氧还蛋白相互作用蛋白通过抑制 NLRP3 炎性小体改善糖尿病视网膜病变的进展。

Elevated microRNA-20b-3p and reduced thioredoxin-interacting protein ameliorate diabetic retinopathy progression by suppressing the NLRP3 inflammasomes.

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhenzhoug, China.

出版信息

IUBMB Life. 2020 Jul;72(7):1433-1448. doi: 10.1002/iub.2267. Epub 2020 Mar 9.

DOI:10.1002/iub.2267
PMID:32150340
Abstract

Over the years, microRNA-20b-3p (miR-20b-3p) has been found to play an essential role in human diseases; we aimed to investigate the effect of miR-20b-3p on the progression of diabetic retinopathy (DR). The DR rat models were established by streptozotocin injection and treated with miR-20b-3p mimics, silenced, or overexpressed thioredoxin-interacting protein (TXNIP). Afterward, the expression of miR-20b-3p and TXNIP, visual function, inflammatory factors, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in rats' retinal tissues were assessed. The target relation between miR-20b-3p and TXNIP was confirmed by dual luciferase reporter gene assay. MiR-20b-3p was poorly expressed while TXNIP was highly expressed in DR rats' retinal tissues. Elevated miR-20b-3p and inhibited TXNIP promoted the visual function, and restricted the inflammatory reaction, microvascular injury, vascular permeability, cell apoptosis, and angiogenesis in DR rats, thereby decelerating the development of DR. Furthermore, TXNIP was targeted by miR-20b-3p. We have found in this study that elevated miR-20b-3p could repress the levels of inflammatory factors by inhibiting TXNIP, thus attenuating the pathology of retina in DR rats, which provided new candidates for DR treatment.

摘要

多年来,miR-20b-3p 在人类疾病中发挥着重要作用;我们旨在研究 miR-20b-3p 对糖尿病视网膜病变(DR)进展的影响。通过链脲佐菌素注射建立 DR 大鼠模型,并采用 miR-20b-3p 模拟物、沉默或过表达硫氧还蛋白相互作用蛋白(TXNIP)进行治疗。然后,评估大鼠视网膜组织中 miR-20b-3p 和 TXNIP 的表达、视觉功能、炎症因子、微血管损伤、血管通透性、细胞凋亡和血管生成。通过双荧光素酶报告基因检测证实了 miR-20b-3p 和 TXNIP 之间的靶关系。DR 大鼠视网膜组织中 miR-20b-3p 表达降低,而 TXNIP 表达升高。升高的 miR-20b-3p 和抑制的 TXNIP 促进了 DR 大鼠的视觉功能,并限制了炎症反应、微血管损伤、血管通透性、细胞凋亡和血管生成,从而减缓了 DR 的发展。此外,miR-20b-3p 是 TXNIP 的靶标。在这项研究中,我们发现升高的 miR-20b-3p 通过抑制 TXNIP 可以抑制炎症因子的水平,从而减轻 DR 大鼠视网膜的病理变化,为 DR 的治疗提供了新的候选药物。

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