TY - JOUR AU - Wang Tian-tian AU - Wu Ling-ling AU - Wu Jie AU - Zhang Li-sheng AU - Shen Wan-jun AU - Zhao Ying-hua AU - Liu Jiao-na AU - Fu Bo AU - Wang Xu AU - Li Qing-gang AU - Bai Xue-yuan AU - Wang Li-qiang AU - Chen Xiang-mei PY - 2023 TI - 14-3-3ζ inhibits maladaptive repair in renal tubules by regulating YAP and reduces renal interstitial fibrosis JF - Acta Pharmacologica Sinica; Vol 44, No 2 (February 2023): Acta Pharmacologica Sinica Y2 - 2023 KW - N2 - 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. UR - http://www.chinaphar.com/article/view/10767