Overexpression Of Noggin In The Lung Epithelium Result In Pulmonary Emphysema

Human emphysema can be classified into congenital emphysema and acquired pulmonary emphysema.Acquired pulmonary emphysema is caused by many kind of postnatal factors such as the bad environment,disease and even the bad habit of smoking and it is a common lung diseases which is a serious threat to human health.We can make mice suffer from acquired pulmonary emphysema to simulate human postnatal pulmonary emphysema by using transgenic method.However,there is no a genetically modified mouse model of congenital emphysema.Establishing the animal model of pulmonary emphysema is very important to explore its pathogenesis.This study used a three transgenic mice system which contain SP-C-rtTA; (tetO)7-Cre; pMES-Noggin and is regulated by the Tet-on system. We over-expressed the Noggin conditionally in the fetal mouse lung epithelium and adult mouse lung epithelium and simulated successfully the congenital and acquired emphysema pathological features that means we have successfully established two kinds of emphysema animal model.The results of this study show that over-Oexpression of Noggin in lung epithelium leading to lung tissue expanded,different sizes of vacuoles formed in the lung edge, some alveolars integrated into a larger cystic cavity and the mean linear intercept(MLI) enlarged. The mean linear intercept of mice which are over-expressed Noggin in the embryonic period (63.38±1.25um) and the adult period (40.62±8.97um) are both larger than the normal mice(9.39±1.25um)and there are significant different(P<0.05).When we detect the expression level of Nox3,which is the emphysema molecular marker,we found that Nox3 protein level in the mutant mice are significantly increased than the normal mice. The mutant mice over-expressed in the embryo was increased by 5 times and the one over-expressed in the adult was increased by 1 time.Further analysis found that,over-expression of Noggin in the lung epithelial result in the WNT/beta -catenin and BMPs/Smad signaling pathway activity levels decreased and destroy the homeostasis of signal transdution and regulation system in the lung.That finally caused the emphysema pathological features.This study successfully established two kinds of mouse emphysema pathological model which is used the gene modified method.This study provides a new effective and reliable animal genetic model for the further study which want to explore the pathogenesis of emphysema and product and screen the specific target drug in the clinical.