Lung Aquaporin Gene Expression And Alveolar Water Transport In Aged Mice

Aquaporins (AQPs) are a family of small and integral membrane proteins that facilitate water transport across cell membranes in response to osmotic gradients. Discovery of AQPs has provided a molecular explanation for rapid water transport across the membranes of many types of cells. AQPs are expressed extensively in the body, including heart, kidney, liver, lung, brain, bone and so on. Also they play a very important role in some physiological and pathophysiological process, such as urine producing.Respiratory system is an important system in the body, which includes trachea, bronchia and alveoli. Respiratory system takes part in gas exchange; immunological defense and air hydration. Among AQPs, AQP1, AQP3, AQP4, and AQP5 are expressed in the respiratory system. Studies show that AQP1 first appears in the lung of rats on the embryonic day 19 and subsequently increases until birth. However, AQP3, AQP4, and AQP5 appear in the lung after birth. The changed expression of AQPs is relative to the changed function of lung before and after birth.It was proposed that clearance of excess fluid from the alveolar space might be decreased with aging. However, its reason is unknown clearly. The purpose of the present study was to examine whether AQPs of lung change in aged mice, whether lung water transport changes and whether the change of lung water transport is associated with the change of AQPs. Since alveolar endothelial water channel AQP1 and alveolar epithelial water channel AQP5 are expressed in peripheral lung and they take part in the process of water transport between alveolar and capillary compartments, they become the main subject in this study. Western blot and RT-PCR analysis was used to detect the expression of AQP1 and AQP5. Both mRNA expression and protein expression of AQP1 and AQP5 are decreased compared with young mice. By a modified gravimetric method, we knew that osmotically and hydrostatically driven water transport rates (Jw) between the airspace and capillary compartments were reduced in aged mice compared with young mice. However, there was no remarkable difference in lung histology between young and aged mice. Subsequently, since corticosteroids can induce expression of AQP1 in the lung, we compared the level of serum glucocorticoid in young mice and aged mice. As expected, there was a dramatic decrease of serum glucocorticoid in aged mice compared with young mice. In vivo administration of dexamethasone (4mg/Kg) to aged mice increased lung AQP1 mRNA and protein expression by about 2 fold, respectively. In addition, decreased water transport rate in the lung also can be increased partially for increased AQP1 expression. However, AQP5 mRNA and protein expression in aged lung was not affected by dexamethasone administration. The present study provided the first evidence of reduced lung water transport rate associated with down-regulation of AQP1 and AQP5 in aged mice. Corticosteroid hormone may accelerate edema clearance in aged lung by stimulating AQP1 expression, providing a new mechanism for using corticosteroid in acute lung edema.