14-3-ζ inhibits maladaptive repair in renal tubules by regulating YAP and reduces renal interstitial fibrosis

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-zeta protein zeta (14-3-3 zeta), 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 14-3-3 zeta in mice using a fluid dynamics-based gene transfection technique. We also overexpressed and knocked down 14-3-3 zeta in vitro. In AKI-CKD model mice, 14-3-3 zeta expression was significantly increased at the AKI stage. During the development of chronic disease, the expression of 14-3-3 zeta tended to decrease, whereas active YAP was consistently overexpressed. In vitro, we found that 14-3-3 zeta 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-zeta slowed the process of renal fibrosis in a mouse model of AKI-CKD. These findings suggest that 14-3-zeta 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.

Automated summary

Acute kidney injury (AKI) is a group of clinical syndromes that may lead to chronic kidney disease (CKD), and the transcriptional coactivator YAP, as well as its regulatory protein 14-3-3 zeta, play important roles in the AKI-CKD transition.