O-连锁β-N-乙酰葡萄糖胺(O-GlcNAc)修饰:糖尿病肾病的新发病机制和治疗靶点。

IF 3.2 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Bingxue Qi, Yang Chen, Siyang Chai, Xiaodan Lu, Li Kang
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引用次数: 0

摘要

目的:O-连接β-N-乙酰葡糖胺(O-GlcNAc)修饰是一种独特的蛋白质翻译后修饰,在糖尿病肾病中会升高。本综述旨在总结目前关于蛋白质的 O-GlcNAcylation 导致糖尿病肾病发病和进展的机制,以及针对 O-GlcNAc 修饰的治疗潜力:方法:对文献中的现有证据进行综述:高血糖增加了进入己糖胺生物合成途径的葡萄糖通量,从而激活了葡糖氨基果糖氨基转移酶的表达和活性,导致肾细胞中产生O-GlcNAc酰化底物UDP-GlcNAc并增加蛋白质的O-GlcNAc酰化。蛋白 O-GlcNAcylation 可调节肾细胞(包括系膜细胞、荚膜细胞和近端肾小管细胞)的功能,并促进肾间质纤维化,导致肾损伤。目前治疗糖尿病肾病的药物,如钠糖共转运体 2(SGLT-2)抑制剂和肾素-血管紧张素-醛固酮系统(RAAS)抑制剂,可延缓疾病进展,抑制蛋白 O-GlcNAcylation:结论:蛋白质 O-GlcNAcylation 的增加会介导肾细胞损伤并促进肾间质纤维化,从而导致糖尿病肾病。虽然目前还不清楚抑制 O-GlcNAcylation 的全部意义,但它可能是治疗糖尿病肾病的一个新靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
O-linked β-N-acetylglucosamine (O-GlcNAc) modification: Emerging pathogenesis and a therapeutic target of diabetic nephropathy.

Aims: O-Linked β-N-acetylglucosamine (O-GlcNAc) modification, a unique post-translational modification of proteins, is elevated in diabetic nephropathy. This review aims to summarize the current knowledge on the mechanisms by which O-GlcNAcylation of proteins contributes to the pathogenesis and progression of diabetic nephropathy, as well as the therapeutic potential of targeting O-GlcNAc modification for its treatment.

Methods: Current evidence in the literature was reviewed and synthesized in a narrative review.

Results: Hyperglycemia increases glucose flux into the hexosamine biosynthesis pathway, which activates glucosamino-fructose aminotransferase expression and activity, leading to the production of O-GlcNAcylation substrate UDP-GlcNAc and an increase in protein O-GlcNAcylation in kidney cells. Protein O-GlcNAcylation regulates the function of kidney cells including mesangial cells, podocytes, and proximal tubular cells, and promotes renal interstitial fibrosis, resulting in kidney damage. Current treatments for diabetic nephropathy, such as sodium-glucose cotransporter 2 (SGLT-2) inhibitors and renin-angiotensin-aldosterone system (RAAS) inhibitors, delay disease progression, and suppress protein O-GlcNAcylation.

Conclusions: Increased protein O-GlcNAcylation mediates renal cell damage and promotes renal interstitial fibrosis, leading to diabetic nephropathy. Although the full significance of inhibition of O-GlcNAcylation is not yet understood, it may represent a novel target for treating diabetic nephropathy.

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来源期刊
Diabetic Medicine
Diabetic Medicine 医学-内分泌学与代谢
CiteScore
7.20
自引率
5.70%
发文量
229
审稿时长
3-6 weeks
期刊介绍: Diabetic Medicine, the official journal of Diabetes UK, is published monthly simultaneously, in print and online editions. The journal publishes a range of key information on all clinical aspects of diabetes mellitus, ranging from human genetic studies through clinical physiology and trials to diabetes epidemiology. We do not publish original animal or cell culture studies unless they are part of a study of clinical diabetes involving humans. Categories of publication include research articles, reviews, editorials, commentaries, and correspondence. All material is peer-reviewed. We aim to disseminate knowledge about diabetes research with the goal of improving the management of people with diabetes. The journal therefore seeks to provide a forum for the exchange of ideas between clinicians and researchers worldwide. Topics covered are of importance to all healthcare professionals working with people with diabetes, whether in primary care or specialist services. Surplus generated from the sale of Diabetic Medicine is used by Diabetes UK to know diabetes better and fight diabetes more effectively on behalf of all people affected by and at risk of diabetes as well as their families and carers.”
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