School of Medicine, University of St Andrews, St Andrews KY16 9TF, UK.
Pathology, Laboratory Medicine, Royal Infirmary of Edinburgh, Little France, Edinburgh EH16 6NA, UK.
Cells. 2023 Aug 29;12(17):2165. doi: 10.3390/cells12172165.
Podocyte cellular injury and detachment from glomerular capillaries constitute a critical factor contributing to kidney disease. Notably, transcription factors are instrumental in maintaining podocyte differentiation and homeostasis. This study explores the hitherto uninvestigated expression of Nuclear Factor Erythroid 2-related Factor 1 (NFE2L1) in podocytes. We evaluated the podocyte expression of NFE2L1, Nuclear Factor Erythroid 2-related Factor 2 (NFE2L2), and NAD(P)H:quinone Oxidoreductase (NQO1) in 127 human glomerular disease biopsies using multiplexed immunofluorescence and image analysis. We found that both NFE2L1 and NQO1 expressions were significantly diminished across all observed renal diseases. Furthermore, we exposed human immortalized podocytes and ex vivo kidney slices to Puromycin Aminonucleoside (PAN) and characterized the NFE2L1 protein isoform expression. PAN treatment led to a reduction in the nuclear expression of NFE2L1 in ex vivo kidney slices and podocytes.
足细胞的细胞损伤和从肾小球毛细血管脱落是导致肾脏疾病的一个关键因素。值得注意的是,转录因子在维持足细胞分化和稳态中起着重要作用。本研究探讨了核因子红细胞 2 相关因子 1(NFE2L1)在足细胞中的表达情况。我们使用多重免疫荧光和图像分析评估了 127 个人类肾小球疾病活检组织中 NFE2L1、核因子红细胞 2 相关因子 2(NFE2L2)和 NAD(P)H:醌氧化还原酶(NQO1)的足细胞表达。我们发现,所有观察到的肾脏疾病中,NFE2L1 和 NQO1 的表达都明显减少。此外,我们将人永生化足细胞和离体肾切片暴露于嘌呤霉素氨基核苷(PAN)中,并对 NFE2L1 蛋白异构体的表达进行了特征描述。PAN 处理导致离体肾切片和足细胞中 NFE2L1 的核表达减少。