Salvage Effect Of Enhanced BMP Signal On Emphysema Caused By Smoke Exposure

Chronic obstructive pulmonary disease(COPD)is a common chronic respiratory disease of human.Emphysema,as the main pathological feature of COPD,has always been the focus of research which focuses on the mechanism of COPD.Emphysema is a characteristic pathological change in the lung parenchyma of COPD patients and is characterized by airflow obstruction caused by destruction of the distal alveolar walls of the terminal fine bronchi.Although the yearly increase in emphysema patients is already a prominent global health problem,there are no treatments that effectively halt the induction or progression of emphysema.Therefore,it is clear that there is a need to develop new therapies to prevent the initiation and the progression of emphysema,and an effective option is through the use of animal models that accurately reflect the physiopathology of the disease,and it is a priority for researchers to apply these findings in the clinic to help patients recover sooner.Long-term smoking is the leading cause of emphysema.Models of smoking animals are currently widely used to study alterations in lung physiology,pathology,and biology.Studies from our laboratory revealed that chronic exposure to CS induces a decrease in the expression level of BMP signaling in mouse lung tissue.This change became more pronounced with longer periods of experimental time.Moreover,enhancing the level of BMP signaling expression in AT2 cells of mice before the onset of smoke exposure could help prevent the development of emphysema in mice.As we know,there are no treatments that effectively halt the induction or progression of emphysema.Further research to explore the therapeutic effect of enhanced BMP signaling in AT2 cells on emphysema caused by cigarette smoke is needed to develop strategies for therapeutic intervention in COPD.In the preliminary stage of this experiment,we found a difference in the alveolar enlargement between mice exposed to smoke for 1 month and mice exposed to smoke for 3 months.Hence,we will use mice exposed to smoke for 1 month or 3 months as the experimental subjects in our study to investigate the therapeutic effects of enhanced BMP signaling activity levels on different degrees of emphysema.To explore the therapeutic effect of enhanced BMP signaling in AT2 cells on emphysema caused by 1-month smoke exposure in mice,we sacrificed lung tissues from four groups of mice: control group,1-month smoke exposure group,1-month smoke exposure no rescue group and 1-month smoke exposure rescue group,and then examined the pathomorphological indicators,inflammation indicators and oxidative stress indicators of these four groups of mice.As the results show,1-month smoke exposure leads to partial degradation of ELASTIN,macrophage clustering and activates inflammatory and oxidative stress and reactive oxygen species and apoptosis that causes alveolar space enlargement and development of emphysema.Even after smoking cessation,these response in the lungs does not stop,but continues to progress.After enhancing the expression level in AT2 cells of BMP mice,the alveoli of the mice returned to normal size,the inflammatory response was curbed,oxidative stress products decreased,apoptotic cells were reduced,the number of AT2 cells and other cells with proliferative capacity was restored,and the cells lost due to smoke exposure were more effectively replaced,thus rescuing their alveolar structural abnormalities to some extent.In order to know the salvage effect of increasing the expression of BMP signal in AT2 cells on emphysema caused by 3-months smoke exposure in mice,we sacrificed lung tissues from four groups of mice: control group,3-months smoke exposure group,3-months smoke exposure no rescue group and 3-months smoke exposure rescue group,and then examined indicators of emphysema of these four groups of mice.It was found that after 3 months of smoke exposure,alveolar vacuolization occurred in the lung tissue of mice,ELASTIN was heavily degraded into protein fragments,macrophages were heavily aggregated,the expression of inflammatory factors was significantly increased,oxidative stress was severe,a large number of cells underwent apoptosis,and the number of cells with proliferative capacity was reduced.After cessation of smoke exposure,various pathological indices of emphysema in mice did not improve,but became more severe.After stopping the smoke exposure and enhancing the expression level of BMP signal in AT2 cells,the degradation of ELASTIN and apoptosis were diminished,however,there was a sustained acute and chronic inflammatory reaction,the content of oxidative stress products continued to increase,the number and proliferation capacity of AT2 cells were not restored to effectively repair the damaged alveolar structures.In summary,enhancing the expression level of BMP signaling in AT2 cells did not rescue severe emphysema caused by chronic smoke exposure in mice.The above results suggest that increasing the expression of BMP signaling in AT2 cells halts mild emphysematous lung destruction caused by 1-month smoke exposure to a certain extent treatment,which can be exploited therapeutically to slow or prevent cigarette smoke-induced emphysema and reduce the severity of inflammation in COPD.