MiR-21-5p promotes RPE cell necroptosis by targeting Peli1 in a rat model of AMD.

IF 1.5 4区 生物学 Q4 CELL BIOLOGY
Yishun Shu, Ziwen Li, Tianyi Zong, Tong Mu, Haoyuan Zhou, Qian Yang, Meili Wu, Yanqiu Liu, Tianhua Xie, Chengye Tan, Miao Zhuang, Xiaolu Wang, Yong Yao
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Abstract

Nonexudative age-related macular degeneration (dry AMD) is characterized by the progressive degeneration of retinal pigment epithelial (RPE) cells and photoreceptors, resulting in central vision loss. The disease is primarily marked by the accumulation of drusen and RPE atrophy. Given the emerging role of miR-21-5p in various ocular diseases, including diabetic retinopathy, glaucoma, pterygium, and choroidal neovascularization, we hypothesized that miR-21-5p may also impact RPE cell integrity in AMD. To test this hypothesis, we employed a rat model of dry AMD induced by sodium iodate (NaIO3) and evaluated the effects of miR-21-5p modulation via intravitreal injections of miR-21-5p agomir or antagomir. Comprehensive assessments were performed using optical coherence tomography (OCT), fundus imaging, histopathology, and biochemical markers. Our results demonstrated an upregulation of miR-21-5p in response to NaIO3 treatment. Administration of miR-21-5p agomir exacerbated RPE damage, while pretreatment with miR-21-5p antagomir mitigated these detrimental effects. Furthermore, in vitro experiments revealed that miR-21-5p regulates necroptosis in CoCl2-treated RPE cells by targeting Pellino1 (Peli1) via its 3' untranslated region, thereby inhibiting Peli1 expression. Overexpression of Peli1 effectively counteracted the necroptotic effects induced by CoCl2. These findings highlight the potential of miR-21-5p as a therapeutic target in dry AMD, expanding our understanding of miRNA-mediated regulation of RPE cells and suggesting new avenues for treatment strategies.

在AMD大鼠模型中,MiR-21-5p通过靶向Peli1促进RPE细胞坏死。
非渗出性年龄相关性黄斑变性(干性AMD)的特征是视网膜色素上皮(RPE)细胞和光感受器的进行性变性,导致中央视力丧失。该疾病的主要特征是肾小球积聚和RPE萎缩。鉴于miR-21-5p在各种眼病中的新作用,包括糖尿病视网膜病变、青光眼、翼状胬肉和脉络膜新生血管,我们假设miR-21-5p也可能影响AMD中RPE细胞的完整性。为了验证这一假设,我们采用了由碘酸钠(NaIO3)诱导的干性AMD大鼠模型,并通过玻璃体内注射miR-21-5p阿戈莫或安他戈莫来评估miR-21-5p调节的效果。采用光学相干断层扫描(OCT)、眼底成像、组织病理学和生化标志物进行综合评估。我们的研究结果表明,miR-21-5p在NaIO3治疗后出现上调。给药miR-21-5p阿哥莫加重了RPE损伤,而miR-21-5p阿哥莫预处理减轻了这些有害影响。此外,体外实验表明,miR-21-5p通过其3'非翻译区靶向Pellino1 (Peli1),从而抑制Peli1的表达,从而调节cocl2处理的RPE细胞的坏死坏死。过表达Peli1可有效抵消CoCl2诱导的坏死作用。这些发现强调了miR-21-5p作为干性AMD治疗靶点的潜力,扩大了我们对mirna介导的RPE细胞调控的理解,并为治疗策略提供了新的途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
3.70
自引率
4.80%
发文量
96
审稿时长
3 months
期刊介绍: In Vitro Cellular & Developmental Biology - Animal is a journal of the Society for In Vitro Biology (SIVB). Original manuscripts reporting results of research in cellular, molecular, and developmental biology that employ or are relevant to organs, tissue, tumors, and cells in vitro will be considered for publication. Topics covered include: Biotechnology; Cell and Tissue Models; Cell Growth/Differentiation/Apoptosis; Cellular Pathology/Virology; Cytokines/Growth Factors/Adhesion Factors; Establishment of Cell Lines; Signal Transduction; Stem Cells; Toxicology/Chemical Carcinogenesis; Product Applications.
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