Airway remodeling: lessons from animal models

Abstract

Airway remodeling, an array of persistent tissue structural changes that occurs through a process of injury and dysregulated repair linked to airway chronic inflammation, is presently believed to largely account for the disease mechanisms of asthma. Increases in airway smooth muscle mass are probably the main mechanism causing airway hyperresponsiveness, and changes in the extracellular matrix may stimulate smooth muscle growth and contribute to the mechanics of airway obstruction. The various components of airway remodeling described inhuman asthma have been successfully reproduced in animal models of several species. Most of the data have been contributed by rat models of allergic sensitization and repeated challenge,transgenic mouse models of cytokine overexpression localized to the lung and, more recently, allergen-driven mouse models using wild-type inbred strains. Overall, animal model shave provided significant insights into the mechanisms of airway remodeling and recent technological developments allow us to exploit these models in new directions. However, the challenge of finding new therapeutic strategies that prevent or control airway remodeling,thus providing etiopathogenically oriented treatments for asthma, still stands. Experimental airway remodeling in animals should be an essential tool for treatment discovery in the near future.