肾脏疾病
纤维化
医学
急性肾损伤
辅活化剂
肾
癌症研究
肾病科
下调和上调
磷酸化
转染
内科学
内分泌学
生物
细胞生物学
基因
转录因子
生物化学
作者
Tiantian Wang,Lingling Wu,Jie Wu,Lisheng Zhang,Weisong Shen,Yinghua Zhao,Jiaona Liu,Bo Fu,Xu Wang,Qinggang Li,Xueyuan Bai,Liqiang Wang,Xiangmei Chen
标识
DOI:10.1038/s41401-022-00946-y
摘要
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.
科研通智能强力驱动
Strongly Powered by AbleSci AI