Department of Nephropathy and Hemodialysis, First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150000, China.
Department of Nephropathy and Hemodialysis, First Affiliated Hospital of Harbin Medical University, No. 23, Youzheng Street, Nangang District, Harbin, Heilongjiang Province, 150000, China.
Biochem Biophys Res Commun. 2022 Jul 23;614:63-69. doi: 10.1016/j.bbrc.2022.04.089. Epub 2022 May 6.
Inflammation and glomerular endothelial dysfunction promote diabetic kidney disease (DKD) progression, 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 mechanism 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-κB (NF-κB) pathway-related proteins were examined. AIF-1 expression was upregulated in glomerular endothelial 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-κB pathway and induced inflammation and oxidative stress. Moreover, this damage could be attenuated by the addition of an NF-κB inhibitor (BAY 11-7082). In conclusion, AIF-1 facilitates glomerular endothelial cell inflammation and oxidative stress in DKD via the NF-κB signaling pathway. Our results provide evidence for the molecular mechanism of DKD and may offer a potential target for DKD treatment.
炎症和肾小球内皮功能障碍促进糖尿病肾病 (DKD) 的进展，但机制尚不完全清楚。同种异体炎症因子-1 (AIF-1) 是一种调节炎症反应和免疫反应的蛋白质。本研究旨在探讨 AIF-1 在 DKD 动物模型和小鼠肾肾小球内皮细胞 (MRGECs) 中的作用机制。我们将 AIF-1-shRNA 注入尾静脉以敲低 db/db 小鼠中的 AIF-1。测量每组的代谢指标、肾脏病理变化和炎症因子。利用慢病毒转染在 MRGECs 中过表达 AIF-1。检测炎症因子、氧化应激和核因子-κB (NF-κB) 通路相关蛋白。db/db 小鼠肾组织中肾小球内皮细胞中 AIF-1 的表达上调。敲低 AIF-1 可逆转 db/db 小鼠的肾损伤和肾炎症。在 30 mM 高糖环境中，MRGECs 中 AIF-1 的过表达激活了 NF-κB 通路，并诱导了炎症和氧化应激。此外，NF-κB 抑制剂 (BAY 11-7082) 的添加可减轻这种损伤。总之，AIF-1 通过 NF-κB 信号通路促进 DKD 肾小球内皮细胞的炎症和氧化应激。我们的研究结果为 DKD 的分子机制提供了证据，并可能为 DKD 的治疗提供了一个潜在的靶点。
