The Pathological Analysis And Genetic Rescue Of Emphysema Mouse SP-C-rtTA;?tetO?₇-Cre;pMes-Noggin

As a common respiratory disease,the main risk factors for pulmonary emphysema are cigarette smoke(CS)and air pollution.The investment for the treatment of pulmonary emphysema are over hundred billion US dollars worldwide annually.Nowadays,the pathogenesis of emphysema still remains unclear.Therefore,it was the difficulty to cure emphysema that threatens the patients' health.Animal models are one of the most efficient approaches to understand the pathophysiological mechanisms.However,the main experimental model of emphysema is congenital or established by stimulating from foreign material at present.The animal models of emphysema failed to simulate the pathological features of acquired emphysema accurately,so that did not find the pathogenesis.Base on previous research,we have established animal model of congenital emphysema depending on Tet-on system,as well as demonstrated the reliability of the animal model from histomorphology and lung function.Because this disease is always clinically found in elderly,comparing with animal model of congenital emphysema,the establishment of acquired emphysema animal model is more meaningful.Then we over-expressed the Noggin conditionally in the adult mouse lung epithelium and found emphysema phenotype.To investigate the pathological process and molecule mechanism of emphysema,this study used SP-C-rtTA;(tetO)7-Cre;pMes-Noggin mice which are fed Dox to overexpress Noggin in the adult mouse lung epithelium.The results of this study shows that overexpression of Noggin in the lung epithelium leading to lung tissue expanded,alveolar septal fractured to form large vacuoles.We detected some pathological indicators in the emphysema mice:imbalance of proteolysis/antiproteolysis,inflammation occurred,oxidative stress occurred and imbalance of proliferation/apoptosis.Further studies suggest that overexpression of Noggin in the lung epithelium down-regulates the expression level of BMP and Wnt signal.Increasing both level of BMP and Wnt signal could rescue emphysema.This study provides a new effective and reliable animal genetic model of acquired emphysema for finding the underlying disease mechanisms,the targeted drug and the new treatment to emphysema.