Aquaporin gene expression and regulation in the ovine fetal lung

Abstract

During fetal life, the future airways of the lung are filled with a liquid that plays a crucial role in the growth and development of the lungs by maintaining them in an expanded state. Lung liquid is secreted across the pulmonary epithelium into the lung lumen due to the osmotic gradient established by the net movement of Cl _ in the same direction. It is not known exactly when lung liquid secretion begins, but fluid is present by midgestation in fetal sheep and is secreted at 2-4 ml kg _1 h _1 between 120 days of gestation and term (~150 days). Fetal lung liquid exits the lungs via the trachea, whereby it is either swallowed (approximately 50 %) or passes directly into the amniotic sac, where it contributes to amniotic fluid volume (Harding & Hooper, 1999).If the fetal trachea is obstructed, which prevents the outward flow of lung liquid, the fetal lung expands with accumulated liquid. This is a potent stimulus for fetal lung growth and also greatly reduces the proportion of type-II alveolar epithelial cells (AECs). Lung liquid drainage on the other hand, deflates the lung, causes lung growth to cease, but increases the proportion of type-II AECs, possibly via type-I to type-II cell differentiation (Flecknoe et al. 2002). As a result it is now widely recognized that the degree to which the fetal lungs are expanded by lung liquid determines the growth and structural development of the lung, as well as the differentiated state of type-I and type-II AECs (Harding & Hooper, 1999). Despite the importance of lung liquid in the development of the lung, the factors controlling the movement of liquid across the pulmonary epithelium have not been fully explored. Furthermore, the effective clearance of lung liquid at birth is vital to allow the entry of air into the lungs with the onset of respiratory gas exchange. This process is largely dependent on the capability of the epithelium to reabsorb large quantities of water.Aquaporins (AQPs) are specific water channels that allow the rapid transcellular movement of water in response to osmotic/hydrostatic pressure gradients (King & Yasui, 2002). At least four AQPs (AQP1, 3, 4 and 5) are expressed in the lungs of various species, including humans, rats, mice and rabbits, although some discrepancies exist in the specific sites of distribution of these proteins. In all species described so far (human, rat, mouse), AQP1 is expressed in the apical and basolateral membrane of the microvascular endothelium and decreased pulmonary vascular permeability has been shown in AQP1-null humans . AQP3 is expressed in the basolateral membrane of basal cells of the tracheal epithelium and in submucosal gland cell membranes in rodents, but is also found in bronchioles (apical membrane) and type-II alveolar Fetal lung development is dependent upon secretion of liquid into the future airways which must be cleared at birth to establish air-breathing. Aquaporins (AQP) 1, 3, 4 and 5 are membranous water channel proteins that are present in the lung after birth in rodents, with little expression be...

Regulation of expression of two aquaporin homologs in the intestine of the European eel: effects of seawater acclimation and cortisol treatment

“…The few reported studies regarding the effect of corticosteroids on AQP expression have only concerned mammalian AQPs, with the steroids upregulating expression in the kidney (33,34,63), the lung (35,36,42,55), the peritoneal epithelium (54), and red blood cells (46). The actions of the corticosteroids on AQP expression in mammals are consistent with the finding presented in this manuscript that cortisol induces upregulation of at least one AQP isoform in the intestine of the European eel.…”

Prenatal Glucocorticoids and Exogenous Surfactant Therapy Improve Respiratory Function in Lambs with Severe Diaphragmatic Hernia Following Fetal Tracheal Occlusion

“…Pulmonary water content remained elevated in DH/TO ϩ S lambs, even when data were adjusted for volume of exogenous surfactant instilled into the airway. Pulmonary epithelial liquid absorption is decreased by TO (36), possibly via altering gene expression of molecular pumps and/or ion channels involved in liquid clearance from the airspaces after birth (37). Regardless, increased pulmonary water content in GC-and surfactant-treated lambs does not seriously impact early neonatal gas exchange.…”

Low Pulmonary Expression of Epithelial Na⁺ Channel and Na⁺, K⁺-ATPase in Newborn Infants with Congenital Diaphragmatic Hernia

“…We observe no significant difference in AQP5 protein expression in CDH infants, even though there is a tendency to a decrease in these patients. AQP5 constitutes a major route for osmotically driven water transport in the ovine lung [12] , but AQP5 knockout in mice is not lethal and shows only moderate pulmonary symptoms at birth [11] . It is plausible that the considerably higher capacity for transcellular water movements in rodents, as compared to humans, represents an important difference between the species.…”

“…Four water channels, aquaporin (AQP) 1, 3, 4 and 5 are also expressed in the lung. AQP5 provides a major route for water movement across the alveolar-capillary interface and is affected by corticosteroids and catecholamines, well-known factors in pulmonary development and function [11][12][13][14] . Respiratory distress syndrome is associated with an inadequate clearance of lung fluid after birth and affected newborns express significantly lower levels of the three ENaC subunits compared to healthy control infants [15] .…”