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晚期糖基化终产物及其可溶性受体在肾脏疾病中的作用。

The Role of Advanced Glycation End Products and Its Soluble Receptor in Kidney Diseases.

机构信息

Nephrology Unit, Department of Internal Medicine and Pediatrics, Ghent University Hospital, 9000 Ghent, Belgium.

Department of Dermatology, Ghent University Hospital, 9000 Ghent, Belgium.

出版信息

Int J Mol Sci. 2022 Mar 22;23(7):3439. doi: 10.3390/ijms23073439.

Abstract

Patients with chronic kidney disease (CKD) are more prone to oxidative stress and chronic inflammation, which may lead to an increase in the synthesis of advanced glycation end products (AGEs). Because AGEs are mostly removed by healthy kidneys, AGE accumulation is a result of both increased production and decreased kidney clearance. On the other hand, AGEs may potentially hasten decreasing kidney function in CKD patients, and are independently related to all-cause mortality. They are one of the non-traditional risk factors that play a significant role in the underlying processes that lead to excessive cardiovascular disease in CKD patients. When AGEs interact with their cell-bound receptor (RAGE), cell dysfunction is initiated by activating nuclear factor kappa-B (NF-κB), increasing the production and release of inflammatory cytokines. Alterations in the AGE-RAGE system have been related to the development of several chronic kidney diseases. Soluble RAGE (sRAGE) is a decoy receptor that suppresses membrane-bound RAGE activation and AGE-RAGE-related toxicity. sRAGE, and more specifically, the AGE/sRAGE ratio, may be promising tools for predicting the prognosis of kidney diseases. In the present review, we discuss the potential role of AGEs and sRAGE as biomarkers in different kidney pathologies.

摘要

患有慢性肾脏病(CKD)的患者更容易受到氧化应激和慢性炎症的影响,这可能导致晚期糖基化终产物(AGEs)的合成增加。由于健康的肾脏大多可以清除 AGEs,因此 AGE 的积累既是由于产量增加,也是由于肾脏清除减少所致。另一方面,AGEs 可能会加速 CKD 患者肾功能的下降,并且与全因死亡率独立相关。它们是非传统风险因素之一,在导致 CKD 患者心血管疾病过多的潜在过程中发挥重要作用。当 AGEs 与其细胞结合受体(RAGE)相互作用时,通过激活核因子 kappa-B(NF-κB)启动细胞功能障碍,增加炎症细胞因子的产生和释放。AGE-RAGE 系统的改变与几种慢性肾脏病的发生有关。可溶性 RAGE(sRAGE)是一种诱饵受体,可抑制膜结合 RAGE 的激活和 AGE-RAGE 相关毒性。sRAGE,特别是 AGE/sRAGE 比值,可能是预测肾脏疾病预后的有前途的工具。在本综述中,我们讨论了 AGEs 和 sRAGE 作为不同肾脏病理生物标志物的潜在作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5543/8998875/99d46f637da7/ijms-23-03439-g001.jpg

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