Department of Pathology, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province , Shijiazhuang, Hebei , China.
Department of Nephrology, The Second Affiliated Hospital of Hebei Medical University , Shijiazhuang, Hebei , China.
Am J Physiol Renal Physiol. 2019 Jan 1;316(1):F186-F194. doi: 10.1152/ajprenal.00218.2018. Epub 2018 Dec 12.
Nudel is a newly discovered factor related to cell migration. The tubular epithelial-mesenchymal transition (EMT) includes four steps: the loss of the adhesive properties of epithelial cells, the acquisition of a mesenchymal cell phenotype, the destruction of the tubular basal membrane, and the migration into the renal interstitium. The purpose of this study was to investigate the role of Nudel in the high-glucose-induced EMT of tubular epithelial cells. Human renal proximal tubular epithelial cells (HKCs) were treated with Nudel shRNA to clarify the role and mechanism of Nudel in tubular EMT induced by high glucose. We found that Nudel was expressed at a high level in high-glucose-stimulated HKCs, and the expression of Nudel was associated with the activation of signal transducer and activator of transcription 3. After transfection with Nudel shRNA, we detected the expression levels of E-cadherin, α-smooth muscle actin (α-SMA), and the Wiskott-Aldrich syndrome family of proteins (including WASP, N-WASP, WAVE1, WAVE2, and WAVE3) via assay. Cell migration was analyzed by the scratching method. The results showed that high glucose downregulated E-cadherin expression, upregulated α-SMA expression, and promoted the migration of HKCs. The expression levels of N-WASP, WAVE1, and WAVE2 were also elevated in HKCs treated with high glucose. All changes induced by high glucose were ameliorated by Nudel depletion. We conclude that Nudel participates in the transition and the migration of tubular epithelial cells via the regulation of WASP family proteins.
Nudel 是一种新发现的与细胞迁移相关的因子。管状上皮-间充质转化（EMT）包括四个步骤：上皮细胞丧失黏附特性、获得间充质细胞表型、管状基底膜破坏以及迁移到肾间质。本研究旨在探讨 Nudel 在高糖诱导的肾小管上皮细胞 EMT 中的作用。用 Nudel shRNA 处理人近端肾小管上皮细胞（HKCs），以阐明 Nudel 在高糖诱导的管状 EMT 中的作用和机制。我们发现 Nudel 在高糖刺激的 HKCs 中高表达，并且 Nudel 的表达与信号转导和转录激活因子 3 的激活有关。转染 Nudel shRNA 后，通过检测 E-钙黏蛋白、α-平滑肌肌动蛋白（α-SMA）和 Wiskott-Aldrich 综合征蛋白家族（包括 WASP、N-WASP、WAVE1、WAVE2 和 WAVE3）的表达水平，划痕法分析细胞迁移。结果表明，高糖下调 E-钙黏蛋白表达，上调 α-SMA 表达，并促进 HKCs 的迁移。高糖处理的 HKCs 中 N-WASP、WAVE1 和 WAVE2 的表达水平也升高。Nudel 耗竭可改善高糖引起的所有变化。我们得出结论，Nudel 通过调节 WAVE 家族蛋白参与管状上皮细胞的转化和迁移。
