Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-κB pathway in diabetic kidney disease
Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-κB pathway in diabetic kidney disease
复制标题
同种异体移植物炎症因子-1 通过 NF-κB 通路增强糖尿病肾病中的炎症和氧化应激
DOI：
10.1016/j.bbrc.2022.04.089
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发表时间：
2022-05-12
影响因子：
3.1
通讯作者：
Hao, Lirong
中科院分区：
文献类型：
--
作者：
Fu, Yuting;Wang, Xingzhi;Hao, Lirong
炎症和肾小球内皮功能障碍促进糖尿病肾病（DKD）的进展，但其机制尚不完全清楚。同种异体移植物炎性因子-1（AIF-1）是一种调节炎症反应和免疫应答的蛋白质。本研究旨在探讨AIF-1在DKD动物模型及小鼠肾小球内皮细胞（MRGECs）中的作用机制。我们将AIF-1-shRNA注射到尾静脉中以敲低db/db小鼠中的AIF-1。检测各组大鼠代谢指标、肾脏病理改变及炎症因子。慢病毒转染用于在MRGEC中过表达AIF-1。检测炎症因子、氧化应激和核因子-κ B（NF-κ B）通路相关蛋白。db/db小鼠肾组织中AIF-1在肾小球内皮细胞中表达上调。敲低AIF-1逆转db/db小鼠的肾损伤和肾脏炎症。在30 mM高葡萄糖环境中，MRGECs中AIF-1的过表达激活了NF-κ B通路并诱导炎症和氧化应激。此外，这种损伤可以通过加入NF-κ B抑制剂（BAY 11-7082）来减弱。总之，AIF-1通过NF-κ B信号通路促进DKD中肾小球内皮细胞炎症和氧化应激。本研究结果为DKD的分子机制提供了证据，并可能为DKD的治疗提供潜在的靶点。(c)爱思唯尔公司All rights reserved.
Inflammation and glomerular endothelial dysfunction promote diabetic kidney disease (DKD) progres-sion, but the mechanisms are not fully understood. Allograft inflammatory factor-1 (AIF-1) is a protein that regulates inflammatory reactions and immune responses. This study aimed to explore the mecha-nism of AIF-1 in a DKD animal model and mouse renal glomerular endothelial cells (MRGECs). We injected AIF-1-shRNA into the tail vein to knockdown AIF-1 in db/db mice. Metabolic index, renal pathological changes and inflammatory factors were measured in each group. Lentiviral transfection was used to overexpress AIF-1 in MRGECs. Inflammatory factors, oxidative stress and nuclear factor-kappa B (NF-kappa B) pathway-related proteins were examined. AIF-1 expression was upregulated in glomerular endo-thelial cells in renal tissues of db/db mice. Knockdown of AIF-1 reversed kidney injury and renal inflammation in db/db mice. In a 30 mM high-glucose environment, overexpression of AIF-1 in MRGECs activated the NF-KB pathway and induced inflammation and oxidative stress. Moreover, this damage could be attenuated by the addition of an NF-kappa B inhibitor (BAY 11-7082). In conclusion, AIF-1 facilitates glomerular endothelial cell inflammation and oxidative stress in DKD via the NF-KB signaling pathway. Our results provide evidence for the molecular mechanism of DKD and may offer a potential target for DKD treatment. (c) 2022 Elsevier Inc. All rights reserved.