2型糖尿病与非糖尿病玻璃体液的比较蛋白质组学分析

Comparative Proteomic Analysis of Type 2 Diabetic versus Non-Diabetic Vitreous Fluids.

作者信息

Alanazi Abdulaziz H, Shan Shengshuai, Narayanan S Priya, Somanath Payaningal R

机构信息

Clinical and Experimental Therapeutics, University of Georgia, Augusta, GA 30912, USA.

Vision Discovery Institute, Augusta University, Augusta, GA 30912, USA.

出版信息

Life (Basel). 2024 Jul 16;14(7):883. doi: 10.3390/life14070883.

DOI:10.3390/life14070883

PMID:39063636

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11278183/

Abstract

BACKGROUND

Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR.

METHODS

Vitreous samples from type 2 diabetic and non-diabetic subjects, collected post-mortem, were analyzed using liquid chromatography-mass spectrometry. Pathway enrichment and gene ontology analyses were conducted to identify dysregulated pathways and characterize protein functions.

RESULTS

Pathway analysis revealed dysregulation in multiple metabolic and signaling pathways associated with diabetes, including glycerolipid metabolism, histidine metabolism, and Wnt signaling. Gene ontology analysis identified proteins involved in inflammation, immune response dysregulation, and calcium signaling. Notably, proteins such as Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), Calcium homeostasis endoplasmic reticulum protein (CHERP), and Coronin-1A (CORO1A) were markedly upregulated in diabetic vitreous, implicating aberrant calcium signaling, inflammatory responses, and cytoskeletal reorganization in DR.

CONCLUSIONS

Our study provides valuable insights into the intricate mechanisms underlying DR and highlights the significance of inflammation, immune dysregulation, and metabolic disturbances in disease progression. Identification of specific proteins as potential biomarkers underscores the multifactorial nature of DR. Future research in this area is vital for advancing therapeutic interventions and translating findings into clinical practice.

摘要

背景

糖尿病视网膜病变（DR）是导致视力丧失的主要原因，其机制复杂。本研究旨在全面探索糖尿病患者和非糖尿病患者的玻璃体液，为确定DR潜在的分子机制铺平道路。

方法

对死后收集的2型糖尿病患者和非糖尿病患者的玻璃体液样本进行液相色谱-质谱分析。进行通路富集和基因本体分析，以识别失调的通路并表征蛋白质功能。

结果

通路分析显示与糖尿病相关的多种代谢和信号通路失调，包括甘油olipid代谢、组氨酸代谢和Wnt信号通路。基因本体分析确定了参与炎症、免疫反应失调和钙信号传导的蛋白质。值得注意的是，2型肌醇1,4,5-三磷酸受体（ITPR2）、内质网钙稳态蛋白（CHERP）和冠蛋白-1A（CORO1A）等蛋白质在糖尿病玻璃体液中显著上调，提示DR中存在异常的钙信号传导、炎症反应和细胞骨架重组。