Bushra Sumbul, Al-Sadeq Duaa W, Bari Redwana, Sahara Afifah, Fadel Amina, Rizk Nasser
Department of Biomedical Sciences, College of Health Sciences, QU-Health, Qatar University, Doha, Qatar.
Biomedical Research Center (BRC), Qatar University, Doha, Qatar.
J Inflamm Res. 2022 May 27;15:3135-3166. doi: 10.2147/JIR.S358594. eCollection 2022.
The pathophysiology of diabetic retinopathy (DR) is multifaced. A low level of circulating adiponectin (APN) in type 2 diabetes is associated with microvasculature complications, and its role in the evolution of DR is complex.
This study is designed to explore the potential impact of APN in the pathogenesis of DR, linking the changes in cellular and biological processes with the pathways, networks, and regulators involved in its actions.
Human microvascular retinal endothelial cells (HMRECs) were exposed to 30mM glucose (HG) and treated with globular adiponectin (30μg/mL) for 24 hours. The cells were evaluated for reactive oxidative stress (ROS) and apoptosis. RT-PCR profile arrays were utilized to evaluate the profile of genes involved in endothelial functions, angiogenesis, extracellular matrix, and adhesion molecules for hyperglycemic HMRECs treated with adiponectin. In addition, the barrier function, leukocyte migration, and angiogenesis were evaluated. The differential expressed genes (DEGs) were outlined, and bioinformatic analysis was applied.
Adiponectin suppresses ROS production and apoptosis in HMRECs under HG conditions. Adiponectin improved migration and barrier functions in hyperglycemic cells. The bioinformatic analysis highlighted that the signaling pathways of integrin, HMGB1, and p38 AMPK, are mainly involved in the actions of APN on HMRECs. APN significantly affects molecular functions, including the adhesion of cells, chemotaxis, migration of WBCs, and angiogenesis. STAT3, NFKB, IKBKB, and mir-8 are the top upstream regulators, which affect the expressions of the genes of the data set, while TNF and TGFB1 are the top regulators.
Adiponectin significantly counteracts hyperglycemia at various cellular and molecular levels, reducing its impact on the pathophysiological progression towards DR in vitro using HMRECs. Adiponectin ameliorates inflammatory response, oxidative stress, and endothelial barrier dysfunction using a causal network of NFBk complex, TNF, and HMGB1 and integrin pathways.
糖尿病视网膜病变（DR）的病理生理学是多方面的。2型糖尿病患者循环脂联素（APN）水平较低与微血管并发症有关，其在DR进展中的作用较为复杂。
本研究旨在探讨APN在DR发病机制中的潜在影响，将细胞和生物学过程的变化与参与其作用的途径、网络和调节因子联系起来。
将人视网膜微血管内皮细胞（HMRECs）暴露于30mM葡萄糖（HG）中，并用球状脂联素（30μg/mL）处理24小时。评估细胞的活性氧化应激（ROS）和凋亡情况。利用RT-PCR谱阵列评估脂联素处理的高血糖HMRECs中参与内皮功能、血管生成、细胞外基质和黏附分子的基因谱。此外，评估屏障功能、白细胞迁移和血管生成。概述差异表达基因（DEGs），并进行生物信息学分析。
脂联素在HG条件下抑制HMRECs中的ROS产生和凋亡。脂联素改善了高血糖细胞的迁移和屏障功能。生物信息学分析表明，整合素、高迁移率族蛋白B1（HMGB1）和p38 AMPK的信号通路主要参与APN对HMRECs的作用。APN显著影响分子功能，包括细胞黏附、趋化性、白细胞迁移和血管生成。信号转导和转录激活因子3（STAT3）、核因子κB（NFKB）、核因子κB抑制蛋白激酶β（IKBKB）和mir-8是影响数据集基因表达的顶级上游调节因子，而肿瘤坏死因子（TNF）和转化生长因子β1（TGFB1）是顶级调节因子。
脂联素在多个细胞和分子水平上显著对抗高血糖，在体外使用HMRECs减少其对DR病理生理进展的影响。脂联素利用NFκB复合物、TNF和HMGB1及整合素途径的因果网络改善炎症反应、氧化应激和内皮屏障功能障碍。
