The Role Of Mitochondrial Fission And Mitophagy In Cigarette Smoke Extract-induced Airway Epithelial Cell Injury Models

Objective The purpose of this study was to elucidate the role and mechanism of mitochondrial fission and mitophagy in cigarette smoke extract(CSE)induced airway epithelial cell injury model.Methods Airway epithelial cells were co-cultured with 5% CSE,pretreated with mitochondrion inhibitor Mdivi-1(Md)and mitophagy inducer Urolithin A(UA).Cell proliferation,oxidative stress,mitochondrial structure,the m RNA levels of inflammatory factor(IL-1,IL-8,IL-18,CXCL1,CXCL8)and necroptosis components(RIPK1,RIPK3,MLKL),mitochondrial fission protein(DRP1,MFF)and mitophagy protein(P62/SQSTM1,LC3B)were examined.Results In Beas 2b cells,5%CSE induced oxidative stress,increased the m RNA expression of inflammatory factor and necroptosis components,induced the destruction in mitochondrial network,increased the protein expression of mitochondrial fission and mitophagy protein p62 / SQSTM1 expression,and decreased mitophagy protein LC3BⅡ/Ⅰ expression.Md/UA pretreatment inhibited oxidative stress,inhibited the expression of inflammatory factor m RNA and necroptosis components m RNA,partially restored mitochondrial network structure,and decreased mitochondrial fission protein level.Md pretreatment increased mitophagy protein P62/SQSTM1 protein level,but did not affect LC3BⅡ/Ⅰ protein expression.Pretreatment with UA inhibited p62 / SQSTM1 protein expression,and increased LC3BⅡ/Ⅰ protein expression.Conclusion The levels of oxidative stress and inflammation increased in airway epithelial cells induced by cigarette smoke.In the injured model of cigarette smoke induced bronchi epithelial cells,mitochondrial fission increased and mitophagy was insufficient.Inhibiting mitochondrial fission or promoting mitophagy can reduce CSE-induced oxidative stress and inflammatory response,and restore mitochondrial structure.