Acute kidney injury (AKI) refers to a group of common clinical syndromes characterized by acute renal dysfunction, which may lead to chronic kidney disease (CKD), and this process is called the AKI-CKD transition. The transcriptional coactivator YAP can promote the AKI-CKD transition by regulating the expression of profibrotic factors, and 14-3-3 protein zeta (14-3-3ζ), an important regulatory protein of YAP, may prevent the AKI-CKD transition. We established an AKI-CKD model in mice by unilateral renal ischemia-reperfusion injury and overexpressed 14-3-3ζ in mice using a fluid dynamics-based gene transfection technique. We also overexpressed and knocked down 14-3-3ζ in vitro. In AKI-CKD model mice, 14-3-3ζ expression was significantly increased at the AKI stage. During the development of chronic disease, the expression of 14-3-3ζ tended to decrease, whereas active YAP was consistently overexpressed. In vitro, we found that 14-3-3ζ can combine with YAP, promote the phosphorylation of YAP, inhibit YAP nuclear translocation, and reduce the expression of fibrosis-related proteins. In an in vivo intervention experiment, we found that the overexpression of 14-3-3ζ slowed the process of renal fibrosis in a mouse model of AKI-CKD. These findings suggest that 14-3-3ζ can affect the expression of fibrosis-related proteins by regulating YAP, inhibit the maladaptive repair of renal tubular epithelial cells, and prevent the AKI-CKD transition.

急性肾损伤（AKI）是指一组以急性肾功能不全为特征的常见临床综合征，可能导致慢性肾脏病（CKD），这一过程称为AKI-CKD转变。转录共激活因子YAP可以通过调节促纤维化因子的表达来促进AKI-CKD转变，而YAP的重要调节蛋白14-3-3蛋白zeta（14-3-3 z）可能阻止AKI-CKD转变。我们通过单侧肾缺血-再灌注损伤建立了小鼠 AKI-CKD 模型，并使用基于流体动力学的基因转染技术在小鼠中过度表达 14-3-3 z。我们还在体外过表达并敲低了 14-3-3ζ。在 AKI-CKD 模型小鼠中，14-3-3ζ 表达在 AKI 阶段显着增加。在慢性疾病的发展过程中，14-3-3 z 的表达趋于减少，而活性 YAP 持续过度表达。在体外，我们发现14-3-3ζ可以与YAP结合，促进YAP磷酸化，抑制YAP核转位，减少纤维化相关蛋白的表达。在体内干预实验中，我们发现14-3-3ζ的过度表达可以减缓AKI-CKD小鼠模型的肾纤维化进程。这些发现提示14-3-3ζ可以通过调节YAP影响纤维化相关蛋白的表达，抑制肾小管上皮细胞的适应不良修复，阻止AKI-CKD转变。