Department of Cardiology and Nephrology, Mie University Graduate School of Medicine, Tsu 514-8507, Mie, Japan.
Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden.
Int J Mol Sci. 2024 May 27;25(11):5808. doi: 10.3390/ijms25115808.
Approximately 30% of steroid-resistant nephrotic syndromes are attributed to monogenic disorders that involve 27 genes. Mutations in family members have also been linked to nephrotic syndrome; however, the precise mechanism remains elusive. To investigate this, podocyte-specific knockout mice were generated to examine phenotypic changes. In the initial assessment under normal conditions, knockout mice showed no significant differences in the urinary albumin-creatinine ratio, blood urea nitrogen, serum creatinine levels, or histological features compared to controls. However, following kidney injury with adriamycin, podocyte-specific knockout mice exhibited a significantly higher albumin-creatinine ratio and a significantly greater sclerotic index than control mice. Electron microscopy revealed more extensive foot process effacement in the knockout mice than in control mice. In addition, -deficient human podocytes showed increased detachment and apoptosis following adriamycin exposure. These findings suggest that KANK1 may play a protective role in mitigating podocyte damage under pathological conditions.
大约 30%的类固醇耐药性肾病综合征归因于涉及 27 个基因的单基因疾病。肾病综合征也与家族成员的突变有关；然而，确切的机制仍难以捉摸。为了研究这一点，生成了足细胞特异性 敲除小鼠以检查表型变化。在正常情况下的初步评估中，与对照组相比， 敲除小鼠的尿白蛋白/肌酐比值、血尿素氮、血清肌酐水平或组织学特征没有明显差异。然而，在用阿霉素引起肾脏损伤后，足细胞特异性 敲除小鼠的白蛋白/肌酐比值显著升高，硬化指数显著高于对照组小鼠。电子显微镜显示，敲除小鼠的足突融合程度比对照组小鼠更严重。此外，在阿霉素暴露后，-缺陷的人足细胞表现出更高的脱离和凋亡。这些发现表明，KANK1 可能在减轻病理条件下的足细胞损伤中发挥保护作用。
