肾小管细胞中Pten的缺失通过上调水通道蛋白2导致水潴留。
Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.
作者信息
Sun Zhuo, Shao Xiaotong, Wu Haotian, Zhao Yaxian, Cao Yidan, Li Danhua, Sun Ying, Wang Qingling
机构信息
Department of Pathology, Laboratory of Clinical and Experimental Pathology, Xuzhou Medical University, Xuzhou, China.
Department of Pathology, Xuzhou Maternity and Child Health Care Hospital, Xuzhou, China.
出版信息
Kidney Dis (Basel). 2022 Nov 29;9(1):58-71. doi: 10.1159/000528010. eCollection 2023 Jan.
INTRODUCTION
Phosphatase and tensin (PTEN) is a multifunctional gene associated with the normal development and physiological function of various tissues including the kidney. However, its role in renal tubular reabsorption function has not been well elucidated.
METHODS
We generated a renal tubule-specific knockout mouse model by crossing mice with transgenic mice, evaluated the effect of loss on renal tubular function, and investigated the underlying mechanisms.
RESULTS
loss resulted in abnormal renal structure and function and water retention in multiple organs. Our results also demonstrated that aquaporin-2 (AQP2), an important water channel protein, was upregulated and concentrated on the apical plasma membrane of collecting duct cells, which could be responsible for the impaired water balance in loss mice. The regulation of loss on AQP2 was mediated by protein kinase B (AKT) activation.
CONCLUSIONS
Our results reveal a connection between gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.
引言
磷酸酶和张力蛋白（PTEN）是一种多功能基因，与包括肾脏在内的各种组织的正常发育和生理功能相关。然而，其在肾小管重吸收功能中的作用尚未得到充分阐明。
方法
我们通过将小鼠与转基因小鼠杂交，构建了肾小管特异性敲除小鼠模型，评估了PTEN缺失对肾小管功能的影响，并探究了其潜在机制。
结果
PTEN缺失导致肾脏结构和功能异常以及多个器官积水。我们的结果还表明，水通道蛋白2（AQP2），一种重要的水通道蛋白，在集合管细胞的顶端质膜上上调并聚集，这可能是PTEN缺失小鼠水平衡受损的原因。PTEN缺失对AQP2的调节是由蛋白激酶B（AKT）激活介导的。
结论
我们的结果揭示了PTEN基因失活与积水之间的联系，表明PTEN在正常肾脏发育和功能中的重要性。
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