p16ink4a deletion switches emphysema to fibrosis in mouse

Introduction: Pulmonary emphysema is an aging-related disease. However, the mechanisms underlying this phenomenon still remain poorly unknown. P16Ink4 is a key factor implicated in aging-related diseases. Whether p16 is involved in elastase-induced emphysema in mice remains to be determined. Aim: To determine if p16 deletion protects against elastase-induced emphysema in mice. Methods: Wild-type (WT) and p16-/- mice were instilled with pancreatic porcine elastase and sacrificed three weeks or three months later to address the degree of emphysema (morphometric analysis), alveolar septal thickness, collagen deposition (sirius red) and myofibroblasts content (α smooth muscle actin immunostaining). Results: Three weeks after instillation, elastase induced airspace enlargement in the same way in WT and p16-/- mice. However, three months later, elastase-instilled WT mice showed airspace enlargement and, without modification of collagen deposition while elastase-instilled p16-/- mice have reduced airspace enlargement, and increased septal thickness with enhanced collagen deposition, and more myofibroblasts. Conclusions: p16-/- mice are not immediately but later protected against elastase-induced emphysema, and develop a concomitant alveolar fibrosis suggesting a process of repair partially defective.