Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> We generated a renal tubule-specific <i>Pten</i> knockout mouse model by crossing <i>Pten</i>^<i>fl/fl</i> mice with <i>Ksp-Cre</i> transgenic mice, evaluated the effect of <i>Pten</i> loss on renal tubular function, and investigated the underlying mechanisms. <b><i>Results:</i></b> <i>Pten</i> 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 <i>Pten</i> loss mice. The regulation of <i>Pten</i> loss on AQP2 was mediated by protein kinase B (AKT) activation. <b><i>Conclusions:</i></b> Our results reveal a connection between <i>PTEN</i> gene inactivation and water retention, suggesting the importance of PTEN in normal kidney development and function.