The Role Of MTOR Signaling Pathway In Lung LyzM~+ Cells

Mammalian target of rapamycin（mTOR）is a serine/threonine kinase in the PI3K family.It acts as an important regulator in protein and lipid biosynthesis,cell cycle process,cell proliferation,survival and aging.The lung is the largest organ in the human body,that is exposed to the environment.In addition to performing the respiratory function,it also has a certain immune function and can clear the invaded foreign pathogens.However,if the external stimulation is too frequent,the lungs are likely to be in a continuous state of inflammation,which will induce pulmonary fibrosis.With the increasing air pollution and the unhealthy lifestyle,idiopathic fibrosis has become more and more common,and this disease has also attracted more and more attention.In recent years,it has been found that the mTOR pathway plays a very important role in the occurrence and development of fibrosis,but how mTOR regulates fibrosis is still unclear.Because mTOR is a protein widely express in various cells,this experiment selected macrophages,which play an important role in pulmonary fibrosis reaction to specifically knock out Tsc1,encoding main inhibitor of the mTOR pathway.We chose LyzM as a marker for macrophages.In the tracing experiments,we found that in addition to macrophages,LyzM can also label type II alveolar cells.After specifically knocking out Tsc1,the cells of mice showed excessive proliferation,especially macrophages and fibroblasts.These cells all play an important role in the process of fibrosis.In the fibrosis model constructed later,pulmonary fibrosis in LyzM-Cre;Tsc1^f/f mice was significantly more severe,indicating that activation of the mTOR pathway in macrophages would make mice more sensitive to fibrosis.And the number of type II alveolar cells shows no difference.Demonstrating link between macrophages and fibrosis.It can also be seen from this study that there is a very close relationship between macrophages and fibroblasts.This finding may provide new ideas for the treatment of lung fibrosis-related diseases.