Airway epithelium wound repair and regeneration after injury

Abstract

The airway epithelium represents the first line of lung defense through different mechanisms such as mucociliary clearance, ion secretion, water regulation and secretion of antibacterial, antiprotease, antioxidant and anti-inflammatory molecules. The intercellular junctional complexes also participate to the preservation of the airway epithelium integrity. Nevertheless, because of its permanent contact with the external milieu, the airway epithelium is frequently injured. Immediately after injury, the airway epithelium initiates a wound healing process to restore its barrier integrity. Several in vitro, ex vivo and in vivo assays have been described to analyze the different steps of wound repair following airway cell damaging. The epithelial process of repair following a wound created in vitro by mechanical or chemical injury is similar to that observed in vivo in animal models. The first and most important event occurring after denudation of the airway epithelium is cell migration and not proliferation. The airway epithelial cells migrate without any external stimulation or non-epithelial cell participation at a speed of about 30-40 microns/h. The cellular and molecular factors involved in wound repair and epithelial regeneration are closely interacting and imply a coordinated sequence of events involving: alteration of the actin cytoskeleton, secretion of extracellular matrix proteins and expression of integrin receptors. Recent human airway xenografts have been developed which have demonstrated that adult airway cells are capable of regenerating a well-differentiated and functional epithelium after successive steps that mimic regeneration after airway epithelium injury. The matrix metalloproteinases are determinant factors in tissue repair by remodeling extracellular matrix and by releasing growth factors. The specific involvement of growth factors such as hepatocyte growth factor in enhancing airway regeneration and repair suggests that these molecules may find future pharmacological application in the treatment of injured airway epithelium.