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<p>Acute kidney injury (AKI) can occur primarily by exposing kidneys to uranium (U). Insulin-like growth factor binding protein 7 (IGFBP7) can regulate sepsis-induced AKI and epithelial-mesenchymal transition through ERK1/2 signaling. In vitro, the IGFBP7’s role and mechanism of action in uranium-induced NRK-52E cells, however, remains unknown. To evaluate the effect of U exposure on kidneys, rat kidney proximal cell line NRK-52E was treated with different concentrations (200, 400, and 800&#xa0;µmol/L) of it. Subsequently, three siRNAs targeting IGFBP7 were transfected with the HiPerFect reagent. The role of the JNK/ERK signaling pathway in uranium-induced kidney cytotoxicity was examined by a series of cell function experiments, including CCK-8 assay, TUNEL staining, RT-qPCR, Western blot, and flow cytometry analysis. Uranium inhibited NRK-52E cell viability and enhanced IGFBP7 expression in a dose-dependent manner. Silencing of IGFBP7 promoted cell cycle progression and inhibited cell apoptosis of uranium-treated cells. Mechanistically, silencing of IGFBP7 inhibited the uranium-activated JNK/ERK signaling pathway. The ERK1/2 signaling inhibitor PD98059 suppressed the IGFBP7-activated JNK/ERK signaling pathway. Furthermore, knockdown of IGFBP7 exerted a similar effect with PD98059 on uranium-induced NRK-52E cell cycle arrest and apoptosis. Silencing IGFBP7 inhibited the JNK/ERK signaling pathway to attenuate uranium-induced cytotoxicity and necrosis of NRK-52E cells.</p>

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Insulin like growth factor binding protein 7 activate JNK/ERK signaling to aggravate uranium-induced renal cell cytotoxicity

  • 期刊论文

  • 发表日期：

    2025年3月1日

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  • Ling Peng,
  • Xi Chen,
  • An-qun Wang,
  • Gang Xie,
  • Bin Zhang,
  • Jia-fu Feng

摘要

Acute kidney injury (AKI) can occur primarily by exposing kidneys to uranium (U). Insulin-like growth factor binding protein 7 (IGFBP7) can regulate sepsis-induced AKI and epithelial-mesenchymal transition through ERK1/2 signaling. In vitro, the IGFBP7’s role and mechanism of action in uranium-induced NRK-52E cells, however, remains unknown. To evaluate the effect of U exposure on kidneys, rat kidney proximal cell line NRK-52E was treated with different concentrations (200, 400, and 800 µmol/L) of it. Subsequently, three siRNAs targeting IGFBP7 were transfected with the HiPerFect reagent. The role of the JNK/ERK signaling pathway in uranium-induced kidney cytotoxicity was examined by a series of cell function experiments, including CCK-8 assay, TUNEL staining, RT-qPCR, Western blot, and flow cytometry analysis. Uranium inhibited NRK-52E cell viability and enhanced IGFBP7 expression in a dose-dependent manner. Silencing of IGFBP7 promoted cell cycle progression and inhibited cell apoptosis of uranium-treated cells. Mechanistically, silencing of IGFBP7 inhibited the uranium-activated JNK/ERK signaling pathway. The ERK1/2 signaling inhibitor PD98059 suppressed the IGFBP7-activated JNK/ERK signaling pathway. Furthermore, knockdown of IGFBP7 exerted a similar effect with PD98059 on uranium-induced NRK-52E cell cycle arrest and apoptosis. Silencing IGFBP7 inhibited the JNK/ERK signaling pathway to attenuate uranium-induced cytotoxicity and necrosis of NRK-52E cells.