Tenascin C knockout mice have an altered lung function at newborn and adult age

Abstract

Introduction: Tenascin C (TNC) is a hexameric extracellular matrix protein. During classical alveolarization, TNC is accumulated at the tips of the growing septa. During adulthood its expression is rather silent and reappears transiently in case of injury, inflammation and wound healing to disappear upon resolution. Previously we demostrated that TNC inactivation negatively affects the development of the bronchial tree and later the process of alveolarization. However, a complete morphological recovery of the lung seems to occur at adult age. Aim: This project aims to study potential functional alterations induced by the absence of TNC. Methods: Five days and three months old wild-type (WT) and tenascin-C knockout (KO) mice were ventilated during one hour with high tidal volume (HTV/40 ml/kg for the newborns or 25 ml/kg for the adults) and compared to WT and KO controls. Pulmonary function parameters were measured using the FlexiVent ventilator. Lung tissue was collected both for molecular biology and histology. Results: Both genotypes showed an increase in static compliance after 1 hour of HTV. However, newborn KO mice started and ended up with a higher static compliance. In adult mice at start of the HTV the same difference in compliance was present. After 1 hour of HTV the compliance increased as expected in WT, but not in KO. We observed a decrease in the thickness of the smooth muscle layer of the bronchioles in 5days and 3 months KO mice and an increase in collagen deposition around the bronchioles in 3 months KO mice. Conclusion: We conclude that absence of TNC not only has an impact on lung function during development but also in adulthood.