BACKGROUND:Mitophagy is closely associated with the development of idiopathic pulmonary fibrosis,but its mechanism remains unclear.OBJECTIVE:To investigate the biological mechanism of mitophagy in idiopathic pulmonary fibrosis and provide ideas for the risk prediction of idiopathic pulmonary fibrosis and subtype differentiation.METHODS:The mitophagy-related genes in idiopathic pulmonary fibrosis were obtained through GEO and Reactome Pathway databases.The mitophagy-related characteristic genes in idiopathic pulmonary fibrosis were screened based on intergroup differences and random forest model.GO functional enrichment analysis and KEGG,Reactome with WIKI pathway enrichment analyses were performed by g:Profiler database.Mitophagy subtypes in idiopathic pulmonary fibrosis were distinguished by consensus clustering method and immune infiltration analysis was performed.The mitophagy-related key gene was screened.Finally,the predictive value of mitophagy-related key gene for the risk of idiopathic pulmonary fibrosis was quantified by alignment diagram and the correlation between mitophagy-related key gene and clinical characteristics of idiopathic pulmonary fibrosis was explored.RESULTS AND CONCLUSION:(1)A total of 13 genes related to mitophagy in idiopathic pulmonary fibrosis were identified and 5 characteristic genes were screened,containing PINK1,RPS27A,SRC,HIF1A,and CDH6.(2)GO analysis was mainly involved in ubiquitin protein ligase binding,and cellular response to hypoxia.Pathway enrichment analysis was mainly involved in PINK1-PRKN mediated mitophagy,NOTCH signaling pathway,signaling by EGFR and angiogenesis.(3)HIF1A had significant expression differences between subtypes,which might serve as a key gene for the differentiation of mitophagy subtypes of idiopathic pulmonary fibrosis.(4)Immune infiltration analysis suggested that myeloid-derived suppressor cell,neutrophil and type 1 T helper cell might have infiltration differences between subtypes,while HIF1A was positively correlated with multiple immune cells.(5)Alignment diagram suggested that the risk of idiopathic pulmonary fibrosis might be predicted by the expression level of HIF1A.(6)Clinical characteristics analysis indicated patients with high expression of HIF1A might have poorer lung function and more severe fibrosis.It is concluded that PINK1,RPS27A,SRC,HIF1A,and CDH6 may influence the development of idiopathic pulmonary fibrosis through mitophagy,in which HIF1A may serve as a key gene for risk prediction with clinical subtype differentiation and HIF1A is strongly associated with the lung function of patients.

BACKGROUND:Mitophagy is closely associated with the development of idiopathic pulmonary fibrosis,but its mechanism remains unclear.OBJECTIVE:To investigate the biological mechanism of mitophagy in idiopathic pulmonary fibrosis and provide ideas for the risk prediction of idiopathic pulmonary fibrosis and subtype differentiation.METHODS:The mitophagy-related genes in idiopathic pulmonary fibrosis were obtained through GEO and Reactome Pathway databases.The mitophagy-related characteristic genes in idiopathic pulmonary fibrosis were screened based on intergroup differences and random forest model.GO functional enrichment analysis and KEGG,Reactome with WIKI pathway enrichment analyses were performed by g:Profiler database.Mitophagy subtypes in idiopathic pulmonary fibrosis were distinguished by consensus clustering method and immune infiltration analysis was performed.The mitophagy-related key gene was screened.Finally,the predictive value of mitophagy-related key gene for the risk of idiopathic pulmonary fibrosis was quantified by alignment diagram and the correlation between mitophagy-related key gene and clinical characteristics of idiopathic pulmonary fibrosis was explored.RESULTS AND CONCLUSION:(1)A total of 13 genes related to mitophagy in idiopathic pulmonary fibrosis were identified and 5 characteristic genes were screened,containing PINK1,RPS27A,SRC,HIF1A,and CDH6.(2)GO analysis was mainly involved in ubiquitin protein ligase binding,and cellular response to hypoxia.Pathway enrichment analysis was mainly involved in PINK1-PRKN mediated mitophagy,NOTCH signaling pathway,signaling by EGFR and angiogenesis.(3)HIF1A had significant expression differences between subtypes,which might serve as a key gene for the differentiation of mitophagy subtypes of idiopathic pulmonary fibrosis.(4)Immune infiltration analysis suggested that myeloid-derived suppressor cell,neutrophil and type 1 T helper cell might have infiltration differences between subtypes,while HIF1A was positively correlated with multiple immune cells.(5)Alignment diagram suggested that the risk of idiopathic pulmonary fibrosis might be predicted by the expression level of HIF1A.(6)Clinical characteristics analysis indicated patients with high expression of HIF1A might have poorer lung function and more severe fibrosis.It is concluded that PINK1,RPS27A,SRC,HIF1A,and CDH6 may influence the development of idiopathic pulmonary fibrosis through mitophagy,in which HIF1A may serve as a key gene for risk prediction with clinical subtype differentiation and HIF1A is strongly associated with the lung function of patients.

Objective:To study the gene expression of nuclear factor erythroid-2-related factor 2 (Nrf2), glutathione-S-transferase (GST) and interleukin-1 β (IL-1β) in A549 cells exposed to hyperoxia and cell apoptosis after siRNA interference with Nrf2.Method:Normal A549 cell lines were assigned into normoxia+siRNA group, normoxia+control group, hyperoxia+siRNA group and hyperoxia+control group according to whether siRNA interference was used and the exposure environment (normoxia/hyperoxia). The hyperoxia environment contained 95%O 2 and 5%CO 2. The levels of mRNA expression of Nrf2, GST and IL-1β were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Flow cytometry was used to examine cell apoptosis of the hyperoxia+control group and hyperoxia+siRNA group at different time points. Analysis of variance (ANOVA) was used to test the relative gene expression and apoptosis of A549 cells. Result:(1) Compared with the normoxia+control group, the expression of Nrf2 and GST in the hyperoxia+control group was significantly increased ( P<0.05), and the expression of IL-1β was significantly decreased ( P<0.05); the expression of Nrf2 and GST in the normoxia+siRNA group decreased significantly ( P<0.05), while the expression of IL-1β increased significantly ( P<0.05). (2) Compared with the normoxia+siRNA group, Nrf2 expression in the hyperoxia+siRNA group showed no significant changes ( P=0.230), GST expression increased slightly ( P=0.057), and IL-1β expression decreased slightly ( P=0.112). (3) Compared with the hyperoxia+control group, the expression of Nrf2 and GST in the hyperoxia+siRNA group decreased significantly ( P<0.05), and the expression of IL-1β increased significantly ( P=0.042). (4) Compared with the hyperoxia+control group, the apoptosis of A549 cells in the hyperoxia+siRNA group increased significantly at 24 h, 48 h and 72 h ( P<0.05). Conclusion:After interfering with Nrf2, siRNA may regulate the expression of GST and IL-1β, preventing oxidative stress, reducing inflammatory response and inhibiting apoptosis.