Liu Chongbin, Yang Ming, Li Li, Luo Shilu, Yang Jinfei, Li Chenrui, Liu Huafeng, Sun Lin
Department of Nephrology, The Second Xiangya Hospital, Central South Unibersity, Changsha, China.
Hunan Key Laboratory of kidney Disease and Blood Purification, Changsha, China.
Front Physiol. 2022 Jul 6;13:909569. doi: 10.3389/fphys.2022.909569. eCollection 2022.
Diabetic kidney disease (DKD) is a common complication of diabetes mellitus and a major cause of end-stage kidney disease (ESKD). The pathogenesis of DKD is very complex and not completely understood. Recently, accumulated evidence from and studies has demonstrated that inflammation plays an important role in the pathogenesis and the development of DKD. It has been well known that a variety of pro-inflammatory cytokines and related signaling pathways are involved in the procession of DKD. Additionally, some anti-hyperglycemic agents and mineralocorticoid receptor antagonists (MRAs) that are effective in alleviating the progression of DKD have anti-inflammatory properties, which might have beneficial effects on delaying the progression of DKD. However, there is currently a lack of systematic overviews. In this review, we focus on the novel pro-inflammatory signaling pathways in the development of DKD, including the nuclear factor kappa B (NF-κB) signaling pathway, toll-like receptors (TLRs) and myeloid differentiation primary response 88 (TLRs/MyD88) signaling pathway, adenosine 5'-monophosphate-activated protein kinase (AMPK) signaling pathways, inflammasome activation, mitochondrial DNA (mtDNA) release as well as hypoxia-inducible factor-1(HIF-1) signaling pathway. We also discuss the related anti-inflammation mechanisms of metformin, finerenone, sodium-dependent glucose transporters 2 (SGLT2) inhibitors, Dipeptidyl peptidase-4 (DPP-4) inhibitors, Glucagon-like peptide-1 (GLP-1) receptor agonist and traditional Chinese medicines (TCM).
糖尿病肾病（DKD）是糖尿病常见的并发症，也是终末期肾病（ESKD）的主要病因。DKD的发病机制非常复杂，尚未完全明确。最近，来自[具体研究1]和[具体研究2]的累积证据表明，炎症在DKD的发病机制和发展过程中起重要作用。众所周知，多种促炎细胞因子和相关信号通路参与了DKD的进程。此外，一些对缓解DKD进展有效的降糖药物和盐皮质激素受体拮抗剂（MRAs）具有抗炎特性，这可能对延缓DKD的进展有益。然而，目前缺乏系统性综述。在本综述中，我们重点关注DKD发生发展过程中的新型促炎信号通路，包括核因子κB（NF-κB）信号通路、Toll样受体（TLRs）和髓样分化初级反应蛋白88（TLRs/MyD88）信号通路、5'-单磷酸腺苷激活蛋白激酶（AMPK）信号通路、炎性小体激活、线粒体DNA（mtDNA）释放以及缺氧诱导因子-1（HIF-1）信号通路。我们还讨论了二甲双胍、非奈利酮、钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂、二肽基肽酶-4（DPP-4）抑制剂、胰高血糖素样肽-1（GLP-1）受体激动剂和中药（TCM）的相关抗炎机制。
