基于四面体框架核酸的DJ-1-saRNA通过抑制铁下垂预防视网膜缺血再灌注损伤。

IF 5.9 1区 生物学 Q2 CELL BIOLOGY
Xianggui Zhang, Zhende Deng, Xiaoxiao Xu, Jingyi Zhu, Zhen Huang, Ya Ye, Jingying Liu, Delun Luo, Jinnan Liu, Ming Yan, Yanping Song
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引用次数: 0

摘要

视网膜缺血/再灌注损伤(RI/RI)是视网膜缺血性疾病的主要病理生理机制,可能导致严重的、不可逆的视力损伤。目前,RI/RI 尚无有效的治疗方法,而氧化应激是导致相关损伤的关键因素。DJ-1是一种重要的内源性抗氧化剂,由于其具有过表达的潜力,因此被认为是治疗RI/RI的一种有前途的药物。本研究利用四面体框架核酸(tFNAs)作为 DJ-1 小激活 RNA(saRNA)的有效传递载体,合成了一种新型纳米复合材料(tFNAs-DJ-1-saRNA)。体外实验表明,tFNAs 能有效地将 DJ-1-saRNA 运送到 R28 细胞中,从而对氧化应激损伤起到修复作用。体内研究发现,tFNAs-DJ-1-saRNA的玻璃体内注射促进了视网膜DJ-1基因的表达,减轻了RI/RI诱导的视网膜萎缩。从机制上讲,tFNAs-DJ-1-saRNA 激活了 xCT/GPX4 通路,从而抑制了铁突变,减少了神经节细胞损伤,保护了视网膜组织。总之,本研究表明,tFNAs-DJ-1-saRNA 复合物可通过抑制铁突变来改善 RI/RI 的病情,这表明它有望成为治疗视网膜缺血性疾病的新型药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Tetrahedral Framework Nucleic Acid-Based Delivery of DJ-1-saRNA Prevent Retinal Ischaemia-Reperfusion Injury via Inhibiting Ferroptosis.

Retinal ischaemia/reperfusion injury (RI/RI) is the primary pathophysiological mechanism underlying retinal ischaemic diseases, potentially resulting in significant and irreversible visual impairment. Currently, there are no effective treatments available for RI/RI, and oxidative stress is a critical factor that contributes to the associated damage. DJ-1, an important endogenous antioxidant, has been proposed as a promising therapeutic agent for RI/RI owing to its potential for overexpression. In this study, tetrahedral frame nucleic acids (tFNAs) were utilised as an effective delivery vehicle for DJ-1 small activating RNA (saRNA), resulting in the synthesis of a novel nanocomposite (tFNAs-DJ-1-saRNA). In vitro experiments demonstrated that tFNAs effectively delivered DJ-1-saRNA to R28 cells, thus exerting a repair effect on oxidative stress injury. In vivo investigations revealed that the intravitreal injection of tFNAs-DJ-1-saRNA facilitated retinal DJ-1 gene expression and mitigated retinal atrophy induced by RI/RI. Mechanistically, tFNAs-DJ-1-saRNA activated the xCT/GPX4 pathway, thereby inhibiting ferroptosis, reducing ganglion cell damage and protecting the retinal tissue. In conclusion, this study demonstrated that the tFNAs-DJ-1-saRNA complex can ameliorate RI/RI by inhibiting ferroptosis, suggesting its potential as a novel agent for the treatment of retinal ischaemic diseases.

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来源期刊
Cell Proliferation
Cell Proliferation 生物-细胞生物学
CiteScore
14.80
自引率
2.40%
发文量
198
审稿时长
1 months
期刊介绍: Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.
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