Aquaporin5 (AQP5) modulation as a novel mechanism to regulate airway barrier function

Abstract

Airflow creates shear forces on the apical surface of airway epithelial cells, the effects of which are largely unknown. In isolated mouse trachea, airflow induced shear stress enhanced epithelial barrier function (permeability of evans blue dye‐4% albumin). Primary human airway epithelial cells differentiated in an air‐interface were exposed to shear stress (3 dynes/cm2) using Krebs solution, leading to increased barrier function (FITC‐dextran permeability) and reduced the abundance of AQP5, an apical water channel, by sequential activation of TRPV4 and VGCC. 16HBE cells, without endogenous AQP5, were infected with either an adeno‐AQP5 expressing or control GFP virus. The presence of AQP5 reduced barrier function and allowed further modulation of barrier function in response to shear stress. Altering barrier function by expressing AQP5 altered receptor‐ligand interactions. Apical ligands (EGF,IFNƒ×) interact with basolateral receptors only when paracellular permeability is increased (induced by AQP5 overexpression). Similarly, Substance P (basolateral ligand) only interacts with apical receptors when AQP5 was overexpressed. We hypothesize that regulation of AQP5 modulates the airway epithelia barrier, which is critical in regulating signaling. This important homeostatic mechanism to regulate epithelial responses may be disrupted in pathologic conditions. Supported by HL085763 and FAMRI.