糖尿病捐献眼视网膜血管周细胞的蛋白质组

IF 3 2区 医学 Q1 OPHTHALMOLOGY Experimental eye research Pub Date : 2024-11-21 DOI:10.1016/j.exer.2024.110178
Sharmila Rajendran, Angayarkanni Narayansamy, Radha Annamalai, Lawrence D Cruze, Kaviarasan Kuppan
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引用次数: 0

摘要

视网膜周细胞(PCs)是一种具有收缩能力的微血管平滑肌细胞,以 1:1 的比例包绕内皮细胞(ECs),维持完整的视网膜血管(RV)。微血管并发症,如慢性糖尿病引起的糖尿病视网膜病变(DR),会导致PC凋亡,随后血管稳定性降低、EC凋亡和缺血,导致视网膜血管生成,最终导致严重的视力丧失。本研究旨在分析从糖尿病供体眼球视网膜血管细胞中分离出的多核苷酸蛋白,并将其与剩余的视网膜血管细胞混合群体(MP)进行比较。研究采用半定量蛋白质组学方法分析了PC和MP蛋白质组。在串联质谱仪上使用 LC-MS/MS 对蛋白质进行提取、定量和重复分析。共鉴定出 42 种 PC 蛋白和 27 种 MP 蛋白,其中 19 种为共用蛋白。功能富集分析表明,PC 蛋白具有共同的生物学过程,如纤维蛋白溶解和 vLDL 颗粒重塑的负调控、一氧化氮转运、磷脂外流、凋亡细胞清除的正调控、软骨细胞增殖、脂蛋白脂肪酶活性以及氧化应激诱导的内在萎缩信号通路。在折叠富集分析中,PC 蛋白与胆固醇代谢、补体和凝血剂、ECM-受体相互作用、长寿调节途径、过氧化物酶体增殖激活受体(PPAR)、病灶粘附和 PI3 Akt 信号通路有关。在PC蛋白中,维生素连接蛋白、凝胶蛋白、角蛋白、脂蛋白A1、C3、H和补体因子C3、C4和C9被鉴定为糖尿病中排名最靠前的蛋白。已发现的视网膜 PC 独特蛋白质可被证明是治疗 DR 的有益靶点。
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Proteome of Pericytes from Retinal Vasculature of Diabetic Donor Eyes.

Retinal pericytes (PCs) are contractile microvascular smooth muscle cells that wrap around the endothelial cells (ECs) maintaining intact retinal vasculature (RV) with a 1:1 ratio. Microvascular complications like Diabetic Retinopathy (DR) due to chronic Diabetes causes apoptotic loss of PCs followed by diminished vessel stability, EC apoptosis, and ischemia, leading to retinal angiogenesis, and eventually severe vision loss. This study aimed to analyze the proteins in PCs isolated from the RV of diabetic human donor eyes and compare them with remaining mixed population (MP) of retinal vascular cells. PCs and MP proteomes were analyzed using semi-quantitative proteomics. Proteins were extracted, quantified, and analyzed in duplicate using LC-MS/MS on a Tandem mass spectrometer. Overall, 42 PC and 27 MP proteins, with 19 shared proteins, were identified. Functional enrichment analysis indicated that PC proteins share common biological processes, such as negative regulation of fibrinolysis and vLDL particle remodeling, nitric oxide transport, phospholipid efflux, positive control over the clearance of apoptotic cells, chondrocyte proliferation, lipoprotein lipase activity, and oxidative stress-induced intrinsic atrophic signaling pathways. In the fold enrichment analysis, the PC proteins were associated with cholesterol metabolism, Complement and coagulant, ECM-receptor interaction, longevity regulating pathway, Peroxisome proliferator-activated receptors (PPAR), focal adhesion and PI3 Akt signaling pathways. Among the PC proteins, vitronectin, gelsolin, hornerin, apolipoprotein A1, C3, H, and complement Factors C3, C4, and C9 were identified as the most highly ranked proteins in diabetes. The identified unique proteins of retinal PC could prove beneficial as a therapeutic target in the management of DR.

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来源期刊
Experimental eye research
Experimental eye research 医学-眼科学
CiteScore
6.80
自引率
5.90%
发文量
323
审稿时长
66 days
期刊介绍: The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.
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