单细胞转录组分析揭示了 Mgarp 在糖尿病视网膜病变中的抗血管生成作用。

IF 3.7 2区 医学 Q2 ENDOCRINOLOGY & METABOLISM BMJ Open Diabetes Research & Care Pub Date : 2024-07-16 DOI:10.1136/bmjdrc-2024-004189
Ling Ren, Jiao Xia, Chang Huang, Yun Bai, Jin Yao, Dan Li, Biao Yan
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引用次数: 0

摘要

导言:糖尿病视网膜病变(DR)是糖尿病常见的血管并发症,也是全球视力丧失的主要原因。在糖尿病视网膜病变的发病机制中观察到了内皮细胞(EC)的异质性。研究设计和方法:我们利用基因表达总库(Gene Expression Omnibus)数据库中的单细胞数据来探讨糖尿病视网膜和非糖尿病视网膜中EC的异质性,并确定参与DR的潜在基因。我们进行了 CCK-8 试验、EdU 试验、transwell 试验和血管形成试验,以确定所识别基因在血管生成效应中的作用:结果:我们的分析确定了视网膜中三种不同的EC亚群,并发现线粒体定位的富谷氨酸蛋白(Mgarp)基因可能与DR的发病机制有关。Silencing of Mgarp significantly suppressed the proliferation, migration, and tube formation capacities in retinal endothelial cells.结论:这项研究不仅为了解视网膜内皮细胞转录组异质性和病理改变提供了新的视角,而且有望为通过靶向视网膜内皮细胞特异性基因进行抗血管生成治疗铺平道路。
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Single-cell transcriptomic analysis reveals the antiangiogenic role of Mgarp in diabetic retinopathy.

Introduction: Diabetic retinopathy (DR) is a common vascular complication of diabetes mellitus and a leading cause of vision loss worldwide. Endothelial cell (EC) heterogeneity has been observed in the pathogenesis of DR. Elucidating the underlying mechanisms governing EC heterogeneity may provide novel insights into EC-specific therapies for DR.

Research design and methods: We used the single-cell data from the Gene Expression Omnibus database to explore EC heterogeneity between diabetic retinas and non-diabetic retinas and identify the potential genes involved in DR. CCK-8 assays, EdU assays, transwell assays, and tube formation assays were conducted to determine the role of the identified gene in angiogenic effects.

Results: Our analysis identified three distinct EC subpopulations in retinas and revealed that Mitochondria-localized glutamic acid-rich protein (Mgarp) gene is potentially involved in the pathogenesis of DR. Silencing of Mgarp significantly suppressed the proliferation, migration, and tube formation capacities in retinal endothelial cells.

Conclusions: This study not only offers new insights into transcriptomic heterogeneity and pathological alteration of retinal ECs but also holds the promise to pave the way for antiangiogenic therapy by targeting EC-specific gene.

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来源期刊
BMJ Open Diabetes Research & Care
BMJ Open Diabetes Research & Care Medicine-Endocrinology, Diabetes and Metabolism
CiteScore
9.30
自引率
2.40%
发文量
123
审稿时长
18 weeks
期刊介绍: BMJ Open Diabetes Research & Care is an open access journal committed to publishing high-quality, basic and clinical research articles regarding type 1 and type 2 diabetes, and associated complications. Only original content will be accepted, and submissions are subject to rigorous peer review to ensure the publication of high-quality — and evidence-based — original research articles.
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