炎症过程调节足细胞中 WT1 的表达和定位，导致肾脏损伤。
The Inflammatory Process Modulates the Expression and Localization of WT1 in Podocytes Leading to Kidney Damage.
机构信息
Department of Microbiology and Immunology, Faculty of Biological Sciences, Autonomous University of Nuevo Leon, Nuevo Leόn, Mexico.
Department of Microbiology and Immunology, Faculty of Biological Sciences, Autonomous University of Nuevo Leon, Nuevo Leόn, Mexico;
出版信息
In Vivo. 2021 Nov-Dec;35(6):3137-3146. doi: 10.21873/invivo.12608.
BACKGROUND/AIM: Wilms' tumor 1 (WT1) is involved in the development of the urogenital system and is expressed in podocytes throughout life. Inflammation of renal glomeruli causes renal damage-induced nephrotic syndrome and steroid-resistant nephrotic syndrome have mutations in the WT1 gene. The aim of this work was to determine if the inflammatory process modulates the expression and localization of WT1 in podocytes that cause kidney damage using lipopolysaccharide (LPS)-treated mice as a sepsis model.
MATERIALS AND METHODS
In investigation of renal damage, proteinuria and histology were analyzed. WT1 modulation was analyzed by indirect immunofluorescence, immunohistochemistry and western blot assays, and proinflammatory cytokines were analyzed by quantitative polymerase chain reaction assay.
RESULTS
WT1 expression decreased most at 24 and 36 h after the induction of inflammation and phosphorylated WT1 was mainly localized in the cytoplasm, reduced nephrin mRNA expression and increased mRNA expression of tumor necrosis factor α and interleukin 1β.
CONCLUSION
These results indicate that the immune system plays an important role in the modulation of WT1, leading to kidney damage.
背景/目的：Wilms 瘤 1（WT1）参与泌尿生殖系统的发育，并在整个生命周期中在足细胞中表达。肾小球炎症导致肾损伤引起的肾病综合征和类固醇耐药性肾病综合征的 WT1 基因发生突变。本研究旨在确定炎症过程是否通过脂多糖（LPS）处理的小鼠作为脓毒症模型来调节导致肾脏损伤的足细胞中 WT1 的表达和定位。
材料和方法
在肾损伤的研究中，分析了蛋白尿和组织学。通过间接免疫荧光、免疫组织化学和 Western blot 检测分析 WT1 的调节，通过定量聚合酶链反应检测分析促炎细胞因子。
结果
炎症诱导后 24 和 36 小时 WT1 表达下降最明显，磷酸化 WT1 主要定位于细胞质，降低了nephrin mRNA 表达，增加了肿瘤坏死因子 α 和白细胞介素 1β 的 mRNA 表达。
结论
这些结果表明免疫系统在 WT1 的调节中起重要作用，导致肾脏损伤。
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