Faculty of Life Science & Medicine, Northwest University, No. 229 Taibai North Road, Xi'an, Shaanxi, 710069, China.
Department of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, No. 2 Xihuamen, Xi'an, Shaanxi, 710003, China.
Free Radic Biol Med. 2021 Aug 1;171:260-271. doi: 10.1016/j.freeradbiomed.2021.05.025. Epub 2021 May 18.
Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease that inevitably progress to end-stage kidney disease. Intervention strategies such as blood glucose control is effective for preventing DKD, but many patients with DKD still reach end-stage kidney disease. Although comprehensive mechanisms shed light on the progression of DKD, the most compelling evidence has highlighted that hyperglycemia-related advanced glycation end products (AGEs) formation plays a central role in the pathogenesis of DKD. Pathologically, accumulation of AGEs-mediated receptor for AGEs (RAGE) triggers oxidative stress and inflammation, which is the major deleterious effect of AGEs in host and intestinal microenvironment of diabetic and ageing conditions. The activation of AGEs-mediated RAGE could evoke nicotinamide adenine dinucleotide phosphate oxidase-induced reactive oxygen and nitrogen species production and subsequently give rise to oxidative stress in DKD and ageing kidney. Therefore, targeting RAGE with its ligands mediated oxidative stress and chronic inflammation is considered as an additional intervention strategy for DKD and ageing kidney. In this review, we summarize AGEs/RAGE-mediated oxidative stress and inflammation signaling pathways in DKD and ageing kidney, discussing opportunities and challenges of targeting at AGEs/RAGE-induced oxidative stress that could hold the promising potential approach for improving DKD and ageing kidney.
糖尿病肾病（DKD）是导致慢性肾脏病不可避免地进展为终末期肾病的主要原因。血糖控制等干预策略对预防 DKD 有效，但许多 DKD 患者仍会发展为终末期肾病。尽管全面的机制阐明了 DKD 的进展，但最有力的证据表明，与高血糖相关的晚期糖基化终产物（AGEs）的形成在 DKD 的发病机制中起着核心作用。在病理上，AGEs 介导的受体（RAGE）介导的 AGEs 积累引发氧化应激和炎症，这是 AGEs 在宿主和糖尿病和衰老条件下的肠道微环境中的主要有害作用。AGEs 介导的 RAGE 的激活可引发烟酰胺腺嘌呤二核苷酸磷酸氧化酶诱导的活性氧和活性氮物种的产生，并随后在 DKD 和衰老肾脏中引起氧化应激。因此，用其配体靶向 RAGE 介导的氧化应激和慢性炎症被认为是 DKD 和衰老肾脏的另一种干预策略。在这篇综述中，我们总结了 DKD 和衰老肾脏中 AGEs/RAGE 介导的氧化应激和炎症信号通路，讨论了靶向 AGEs/RAGE 诱导的氧化应激的机会和挑战，这可能为改善 DKD 和衰老肾脏提供有前景的方法。
