International Joint Laboratory for Embryonic Development & Prenatal Medicine, Division of Histology and Embryology, Medical College, Jinan University, Guangzhou, China.
Department of Pathology, First Affiliated Hospital of Jinan University, Guangzhou, China.
Nephrol Dial Transplant. 2024 Nov 27;39(12):1993-2004. doi: 10.1093/ndt/gfae090.
Activation of nuclear factor-kappa B (NF-κB) signalling is key in the pathogenesis of chronic kidney disease (CKD). However, a certain level of NF-κB activity is necessary to enable tissue repair.
The relationship between activated and inactivated NF-κB signaling and the pathogenesis of CKD was investigated using mouse models of NF-κB partial inactivation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into alanine) and activation (mutating cysteine at position 59 of the sixth exon on the NF-κB gene into serine).
The density of CD3, CD8, CD68 positive cells, as well as the expression of interleukin 6, Tumor necrosis factor receptor associated factor 1 and Nef-associated factor 1 in the kidney tissues of NF-κBC59A mice were reduced, whereas an opposing pattern was observed in the NF-κBC59S mice. Blood pressure, kidney fibrosis (analyzed by periodic acid-Schiff, Masson trichrome and Sirius Red staining, as well as α-SMA immunofluorescence), serum creatinine and urinary albumin-to-creatinine ratio are markedly increased in NF-κB-activated and -inactivated mice compared with controls. Transmission electron microscopy indicated that the glomerular basement membrane was thicker in both NF-κBC59A and NF-κBC59S mice compared with wild-type mice.
Using mice models with partially activated and inactivated NF-κB pathways suggests that there is an apparently U-shaped relationship between blood pressure, kidney function as well as morphology and the activation of the NF-κB pathway. A certain optimal activity of the NF-κB pathway seems to be important to maintain optimal kidney function and morphology.
核因子-κB（NF-κB）信号的激活是慢性肾脏病（CKD）发病机制中的关键。然而，NF-κB 活性的一定水平对于组织修复是必要的。
使用 NF-κB 部分失活（将 NF-κB 基因第六外显子 59 位的半胱氨酸突变为丙氨酸）和激活（将 NF-κB 基因第六外显子 59 位的半胱氨酸突变为丝氨酸）的小鼠模型，研究了激活和失活的 NF-κB 信号与 CKD 发病机制之间的关系。
NF-κBC59A 小鼠肾组织中 CD3、CD8、CD68 阳性细胞密度以及白细胞介素 6、肿瘤坏死因子受体相关因子 1 和 Nef 相关因子 1 的表达减少，而 NF-κBC59S 小鼠则观察到相反的模式。与对照组相比，NF-κB 激活和失活的小鼠血压、肾脏纤维化（通过过碘酸希夫、马松三色和天狼星红染色以及α-SMA 免疫荧光分析）、血清肌酐和尿白蛋白/肌酐比值显著增加。透射电子显微镜显示，与野生型小鼠相比，NF-κBC59A 和 NF-κBC59S 小鼠的肾小球基底膜更厚。
使用 NF-κB 途径部分激活和失活的小鼠模型表明，血压、肾功能以及形态与 NF-κB 途径的激活之间存在明显的 U 型关系。NF-κB 途径的一定最佳活性对于维持最佳肾功能和形态似乎很重要。
