Inflammatory Factors Induced Autophagy Regulation In Placental MSCs Treatment Of Acute Lung Injury

Acute lung injury(ALI)pathogenesis is complex,and no special treatment program.Mesenchymal stem cells(MSCs),as pluripotent precursor cells with self-renewal potential and multi-directional differentiation potential,bring the treatment of ALI A new idea.The cell characteristics and function of mesenchymal stem cells have certain plasticity,that is,changes with the microenvironment,so that their biological function in the basic research and clinical application of the complexity and diversity of the characteristics.What cell characteristics and functions of mesenchymal stem cells play an inflammatory environment in acute lung injury remains to be studied.Objective:To study the effect of autophagy on the treatment of acute lung injury in MSCs in inflammatory environment.Methods:(1)The healthy placenta was obtained from the general hospital of Ningxia Medical University.The mesenchymal stem cells were identified and cultured according to the established culture of mesenchymal stem cells.(2)The expression of autophagy-labeled protein LC3 I / II,Atg5 and Atg7 were detected by western blot in the presence of IL-1?,IL-6,IFN-? and TNF-? inflammatory factors.Treatment of human placental-derived mesenchymal stem cells with IL-1?,IL-6,IFN-? and TNF-? inflammatory factors to observe cell proliferation.Application of autophagy inhibitor 3-MA and inflammatory factor in the treatment of human placental-derived mesenchymal stem cells to observe cell proliferation.(3)The expression of apoptosis-related markers Caspase3 and PARP1 were detected by western blot.(4)Human placental-derived mesenchymal stem cells,which were infected with si-NC and si-Atg7 lentiviruses,were injected into mice via tail vein,in the model of acute lung injury induced by bleomycin(BLM)in mice.We observe the survival rate of mesenchymal stem cells in mice with acute lung injury and observe the pathological changes of lung tissue.Results:(1)We successfully isolated and cultured human placental derived mesenchymal stem cells.(2)Inflammatory factors IL-1?,IL-6,IFN-? and TNF-? can induce autophagy of MSCs,in which IFN-? and TNF-?-induced autophagic inhibition of cell proliferation.Inhibition of IFN-? and TNF-?-induced autophagy can restore the proliferation of mesenchymal stem cells.(3)Inflammatory factors IFN-?,TNF-? induced MSC apoptosis due to autophagy.(4)In the mice model of acute lung injury induced by bleomycin(BLM),the si-Atg7 group had a higher survival rate and more obvious pathological changes in lung tissue compared with the si-NC group.Conclusion:(1)Inflammatory factors IL-1?,IL-6,IFN-? and TNF-? induce autophagy in mesenchymal stem cells.(2)IFN-? and TNF-? can induce mesenchymal stem cells autophagy,resulting in apoptosis of mesenchymal stem cells,reducing the survival rate of mesenchymal stem cell transplantation,affecting the therapeutic effect of mesenchymal stem cells on acute lung injury.