Alteration of autophagy-related protein 5 (ATG5) levels and Atg5 gene expression in diabetes mellitus with and without complications.

IF 2.8 4区医学 Q3 ENDOCRINOLOGY & METABOLISM

Diabetes & Vascular Disease Research Pub Date : 2021-11-01 DOI:10.1177/14791641211062050

Remah Yassin, Hagar Tadmor, Evgeny Farber, Anas Igbariye, Aida Armaly-Nakhoul, Inbal Dahan, Farid Nakhoul, Nakhoul Nakhoul

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引用次数: 0

Abstract

Background: Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary intracellular components and responsible for normal cellular homeostasis. Autophagy pathway and its key participant ATG5/LC3 are associated with several pathologies such as diabetes mellitus and its complications.

Methods: Levels and expression of autophagy key components ATG5 and LC3B were analyzed in both human model and murine tissues. One hundred and twenty human subjects were divided into four groups: Healthy (control), diabetes mellitus without complications, diabetic nephropathy, and diabetic retinopathy. Additionally, we used kidneys from WT healthy and diabetic nephropathy mice. Lysate derived from human peripheral blood mononuclear cells and murine renal cortex lysates were subjected to western blot and immunohistochemical analysis.

Results: Western blot and immunohistochemical analysis demonstrate that ATG5 protein levels were significantly decreased in diabetes mellitus, diabetic nephropathy (DN), and diabetic retinopathy patients versus healthy controls and in DN mice compared to healthy mice (0.65 ± 0.04; 1.15 ± 0.13 A.U. units, respectively). Quantification of staining area (%) of ATG5 mice tissue expression also decreased in DN versus healthy mice (4.42 ± 1.08%; 10.87 ± 1.01%, respectively).

Lc3b levels and expression: Significant reduction in peripheral blood mononuclear cells in diabetic patients (with or without complications) vs. healthy controls. Renal LC3B levels were lower in DN versus healthy mice (0.36 ± 0.03; 0.68 ± 0.07 A.U. units). Renal LC3B staining quantification revealed significant reduction in DN versus healthy mice (1.7 ± 0.23%; 8.56 ± 1.7%).

Conclusion: We conclude that ATG5, as well as LC3B, are down regulated in diabetic patients with or without complications. This diminution contributes to deficiencies in the autophagy process.

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伴有或不伴有并发症的糖尿病患者自噬相关蛋白 5 (ATG5) 水平和 Atg5 基因表达的变化。

背景：自噬是一种分解代谢机制，包括依赖溶酶体降解细胞内不必要的成分，并负责正常的细胞平衡。自噬途径及其关键参与者 ATG5/LC3 与糖尿病及其并发症等多种病症有关：方法：分析人体模型和小鼠组织中自噬关键成分 ATG5 和 LC3B 的水平和表达。我们将 120 名人类受试者分为四组：健康组（对照组）、无并发症糖尿病组、糖尿病肾病组和糖尿病视网膜病变组。此外，我们还使用了 WT 健康小鼠和糖尿病肾病小鼠的肾脏。对人外周血单核细胞裂解液和小鼠肾皮质裂解液进行了 Western 印迹和免疫组化分析：Western印迹和免疫组化分析表明，与健康对照组相比，糖尿病、糖尿病肾病（DN）和糖尿病视网膜病变患者的ATG5蛋白水平明显下降；与健康小鼠相比，DN小鼠的ATG5蛋白水平也明显下降（分别为0.65 ± 0.04；1.15 ± 0.13 A.U.单位）。ATG5小鼠组织表达的染色面积定量（%）在DN与健康小鼠相比也有所下降（分别为4.42 ± 1.08%; 10.87 ± 1.01%）：与健康对照组相比，糖尿病患者（无论有无并发症）外周血单核细胞中的 LC3B 水平显著降低。与健康小鼠相比，DN 肾脏 LC3B 水平较低（0.36 ± 0.03；0.68 ± 0.07 A.U. 单位）。肾脏LC3B染色定量显示，DN与健康小鼠相比显著降低（1.7 ± 0.23%; 8.56 ± 1.7%）：我们得出的结论是，无论是否有并发症，糖尿病患者体内的 ATG5 和 LC3B 都受到了调控。结论：我们得出的结论是，无论是否有并发症，糖尿病患者体内 ATG5 和 LC3B 的调节能力都会下降，这种下降导致自噬过程出现缺陷。

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来源期刊

Diabetes & Vascular Disease Research ENDOCRINOLOGY & METABOLISM-PERIPHERAL VASCULAR DISEASE

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： Diabetes & Vascular Disease Research is the first international peer-reviewed journal to unite diabetes and vascular disease in a single title. The journal publishes original papers, research letters and reviews. This journal is a member of the Committee on Publication Ethics (COPE)