School of Nursing, Xiangnan University, Chenzhou, China.
Department of Medicine, Xiangnan University, Chenzhou, China.
Anal Cell Pathol (Amst). 2022 Jun 27;2022:8213683. doi: 10.1155/2022/8213683. eCollection 2022.
Acute kidney injury (AKI) is an important public health concern and characterized as tubular death involved in apoptosis and necrosis. Autophagy is rapidly induced in tubules and associates with renal tubular cells homeostasis to have a complex link with tubular death in AKI. Numb is a multifunctional protein and exerts protective role in tubular death in AKI induced by Cisplatin. However, the effect of Numb on tubular autophagy remains to be investigated. In the present study, the protein expression of LC3 and Beclin-1 related to autophagy was analyzed in Cisplatin-induced AKI mice with knocking down Numb. In model of tubular injury induced by Cisplatin , downregulation of Numb in NRK-52E cells also inhibited the activation of autophagy accompanied with the decreased protein level of p53. Overexpression of Numb in NRK-52E cells activated autophagy with increased LC3 and Beclin-1 expression accompanied with increased protein level of p53. Moreover, autophagy activation following Numb overexpression was suppressed by p53 inhibitor pifithrin-. These data indicate that Numb promotes p53-mediated activation of tubular autophagy in AKI induced by Cisplatin and therefore may provide important targets for the treatment of AKI.
急性肾损伤 (AKI) 是一个重要的公共卫生关注点，其特征为涉及细胞凋亡和坏死的肾小管死亡。自噬在肾小管中迅速被诱导，并与肾小管细胞的稳态相关联，与 AKI 中的肾小管死亡有复杂的联系。Numb 是一种多功能蛋白，在顺铂诱导的 AKI 中的肾小管死亡中发挥保护作用。然而，Numb 对肾小管自噬的影响仍有待研究。在本研究中，通过敲低 Numb 分析了与自噬相关的 LC3 和 Beclin-1 在顺铂诱导的 AKI 小鼠中的蛋白表达。在顺铂诱导的肾小管损伤模型中，NRK-52E 细胞中 Numb 的下调也抑制了自噬的激活，同时伴随着 p53 蛋白水平的降低。NRK-52E 细胞中 Numb 的过表达激活了自噬，LC3 和 Beclin-1 的表达增加，同时 p53 蛋白水平增加。此外，p53 抑制剂 pifithrin-抑制了 Numb 过表达后的自噬激活。这些数据表明，Numb 促进了顺铂诱导的 AKI 中 p53 介导的肾小管自噬的激活，因此可能为 AKI 的治疗提供重要靶点。
