Kidney tubular transcription co-activator, Yes-associated protein 1 (YAP), controls the expression of collecting duct aquaporins and water homeostasis

• DOI: 10.1016/j.kint.2022.10.007
• Publication Date: 2022-11-01T01:10:47Z
• Authors: Yu Zhang; Huihui Huang; Yonglun Kong; Chunhua Xu; Liujiang Dai; Xiaoqiang Geng; Yujie Deng; Yang Wang; Yang Liu; Chenling Meng; Xiaoyi Zhang; Jinhong Li; Jinzhong Qin; Bo Feng; Kingston Kinglun Mak; Li Wang; Yu Huang; Weidong Wang; Hui-Yao Lan; Baoxue Yang; Hua A. Jenny Lu; Yin Xia
• Keywords: Aquaporin 2; Homeostasis; Transcription

Final urine volume and concentration are defined by water reabsorption through the channel proteins aquaporin (AQP)-2, -3 -4 in collecting duct. However, transcriptional regulation of these AQPs is not well understood. The Hippo/Yes-associated protein 1 (YAP) pathway plays an important role organ size control tissue homeostasis. When Hippo including Mst1/Mst2 kinases inhibited, YAP activated functions as a transcription co-activator. Our previous work revealed pathological tubular activation chronic kidney disease, but physiological remains to be established. Here, we found that tubule-specific Yap knockout mice showed increased output decreased urinary osmolality. Decreases Aqp2, mRNA abundance were evident mice. Analysis double Mst1/Mst2/Yap triple expression Aqp2 Aqp4 Aqp3 was dependent on YAP. Furthermore, recruited promoters genes stimulated their transcription. Interestingly, interact with factors GATA2, GATA3 NFATc1. These three promoted manner duct cells. also whereas only GATA2 enhanced Thus, our results suggest promotes transcription, interacts NFATc1 expression, while Aqp-2, exploit overlapping mechanisms for baseline regulation.