Molecular mechanisms of cell death in bronchopulmonary dysplasia

Deng, Xianhui; Bao, Zhidan; Yang, Xianpeng; Mei, Yingzi; Zhou, Qin; Chen, Ailing; Yu, Renqiang; Zhang, Yongjun

doi:10.1007/s10495-022-01791-4

Cited by 19 publications

(13 citation statements)

References 158 publications

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“…Included in the pathogenesis of BPD are activation of Notch4, elevated serum SENP1 protein expression, and decreased SIRT1 expression, changes that promote P53 acetylation and Bax expression, which promotes apoptosis, as well as inhibition of ERK1/2 under hyperoxic conditions, which damages the vasculature and increases apoptosis and necrosis mainly associated with RIRP3 and MLKL. Activation of RIRP3, when activated, binds to NF-κB, and a series of molecular mechanisms impede alveolar development, leading to increased in ammatory responses, resulting in cell necroptosis and impaired alveolar function, but autophagy-associated Pink1/Parkin signaling reduces in ammation and improves lung function, and it is believed that a high-oxygen environment contributes signi cantly to the development of BPD through various cellular death processes [44]. Apoptosis and autophagy are signi cantly correlated and play important roles in maintaining the structural and functional integrity of the lungs as important biological events in maintaining the homeostasis of the internal environment of the animal body.…”

Section: Discussionmentioning

confidence: 99%

Effect of transport stress on apoptosis and autophagy in goat lung cells

Zhuo,

Hu,

Liu

et al. 2024

Preprint

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Background Goats undergoing road transportation are subjected to inverse organismal disturbances in the external environment, with high temperatures, bumps, and complex microbial environments during transportation linking to compound stressors, which can trigger pathological apoptosis and autophagy. Pathological cell death dysregulating the homeostasis of the internal environment of the organism and thus causing immunosuppression and tissue damage. Bcl-2 and Bax are a pair of functional antagonistic proteins regulating apoptosis, p62, LC3B and the PINK1/Parkin pathway have also been shown to play important mediating roles in the process of cellular autophagy. The aim of this study was to investigate the effects of transportation stress on proteins related to apoptosis and autophagy in goat lung cells. Nine healthy male Ganxi goats were selected and divided into control group without transport (0h transport group), 2h transport group, 6h transport group, three in each group, and the lungs were taken after treatment. Results The results of the study showed that transportation stress increased the apoptosis rate in goat lungs, which was significantly higher in the 2h transportation group than in the 6h transportation group and the control group. Apoptotic proteins Bcl-2 and Bax were mainly expressed in the bronchial epithelium at all levels as well as in the alveolar septum. Autophagy-associated LC3B proteins were distributed in the cytoplasm of alveoli and bronchioles, and p62, PINK1 and Parkin proteins were widely expressed in the alveolar epithelium and the cytoplasm of cells in specific sites and nuclei. Also, there was a significant downregulation of PINK1 and Parkin proteins after the 6h transportation. Apoptosis-associated Bcl-2 and Bax genes and autophagy-associated LC3B, p62, PINK1 and Parkin genes showed different degrees of dysregulation after a certain time of transport, respectively. Conclusion The results of our study indicate that transportation stress could lead to an up-regulation of apoptosis rate in goat lung cells, which exhibited both a significant effect on the expression levels of apoptosis-related Bcl-2 and Bax genes, and triggered a dysregulation of autophagy-related LC3B, p62, PINK1 and Parkin genes, suggesting that transportation stress is closely related to apoptosis and autophagy in the lungs of goats.

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Section: Discussionmentioning

confidence: 99%

Effect of transport stress on apoptosis and autophagy in goat lung cells

Zhuo,

Hu,

Liu

et al. 2024

Preprint

View full text Add to dashboard Cite

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“…There existed a decrease in the number of cells in the model group with variable changes in cell morphology during the construction of a hyperoxic BPD cell model, and also detected a decrease in GPX4 mRNA expression and an upregulation of PTGS2 expression in the model group, which has not been reported before. In addition, Cross et al (18, 19) reported that free iron concentrations in cord blood were significantly higher in preterm infants than in full-term infants and adults. Patel et al (20) reported that increased cumulative iron supplementation in very low birth weight infants is an independent risk factor for BPD.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analyses and experimental validation of ferroptosis-related genes in bronchopulmonary dysplasia pathogenesis

Luo,

Zhang,

et al. 2023

Preprint

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ObjectiveWe aimed to study the involvement of ferroptosis in the pathogenesis of bronchopulmonary dysplasia (BPD) by conducting bioinformatics analyses and identifying and validating the associated ferroptosis-related genes to explore new directions for treating BPD.MethodsThe dataset GSE32472 on BPD was downloaded from the public genome database. Using R language, differentially expressed genes (DEGs) between the BPD and normal group were screened. In the present study, we adopted weighted gene correlation network analysis (WGCNA) for identifying BPD-related gene modules and ferroptosis-related genes were extracted from FerrDb. Their results were intersected to obtain the hub genes. After that, to explore the hub gene-related signaling pathways, the hub genes were exposed to gene ontology enrichment analysis. With the purpose of verifying the mRNA expression of the hub genes, a single-gene gene set enrichment analysis and quantitative reverse transcription polymerase chain reaction were conducted. Immune cell infiltration in BPD was analyzed using the CIBERSORT inverse fold product algorithm.ResultsA total of 606 DEGs were screened. WGCNA provided the BPD-related gene module darkgreen4. The intersection of DEGs, intramodular genes, and ferroptosis-related genes revealed six ferroptosis-associated hub genes (ACSL1,GALNT14,WIPI1,MAPK14,PROK2, andCREB5). Receiver operating characteristic curve analysis demonstrated that the hub genes screened for BPD were of good diagnostic significance. According to the results of immune infiltration analysis, the proportions of a cluster of differentiation (CD)8, CD4 naive, and memory resting T cells and M2 macrophage were elevated in the normal group, and the proportions of M0 macrophage, resting mast cell, and neutrophils were increased in the BPD group.ConclusionsA total of six ferroptosis-associated hub genes in BPD were identified in this study, and they may be potential new therapeutic targets for BPD.

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“…IL6T is the receptor of cytokines IL-6 and IL-27. A large number of studies have shown that IL-6 level is closely related to the severity of BPD disease [29]. Meanwhile IL-27 plays an important role in innate immune cells such as lymphocytes and macrophages through different signaling pathways and cytokines, leading to the occurrence of BPD [30], IL-27 can also regulate Th1-type and Th2-type immune responses and affect CD8 T cell response [31,32], while CD8 T cell and Th1, Th2 immune responses were involved in the occurrence of BPD [33].…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of characteristic genes of inflammation-related bronchopulmonary dysplasia based on bioinformatics methods

An,

2023

Preprint

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Background: Bronchopulmonary dysplasia (BPD) is the most common complication of premature infants, and inflammation plays an important role in it. In this research, the key genes of inflammation-related BPD were comprehensively analyzed by bioinformatics methods, and a prediction model was constructed. Methods: We obtained the GSE188944 and GSE108794 datasets from the GEO database and conducted GO and KEGG enrichment analyses to identify differential genes associated with inflammation-related BPD. Through the implementation of LASSO regression, RF, and XGBOOST algorithms, identify the key genes. The accuracy of these key genes in predicting BPD was assessed using ROC curve analysis and AUC calculations. In addition, the GSE190215 data set is used for external verification. Furthermore, we performed GSEA to quantify the key genes and analyze pathways, examine immune cell infiltration in BPD tissues, and explore the correlation amongst the key genes. Additionally, we used relevant databases to predict the miRNA and transcription factors associated with the key genes. Results: This study successfully identified seven key genes (HLA-DRB1, SLC39A8, IL2RA, SYK, CD180, IL6ST, IL18R1) as novel markers for constructing a diagnostic prediction model for BPD. GSEA analysis revealed enrichment pathways related to the key genes, and significant differences in the infiltration of CD8+ T cells, natural killer cells, and mast cells were observed between BPD and non-BPD samples. Conclusion: We successfully developed a risk model for inflammation-related BPD key genes, displaying favorable verification performance, but poor external verification performance. These findings suggest that inflammatory genes may influence the occurrence and progression of BPD through immune cell infiltration.

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Molecular mechanisms of cell death in bronchopulmonary dysplasia

Cited by 19 publications

References 158 publications

Effect of transport stress on apoptosis and autophagy in goat lung cells

Effect of transport stress on apoptosis and autophagy in goat lung cells

Bioinformatics analyses and experimental validation of ferroptosis-related genes in bronchopulmonary dysplasia pathogenesis

Comprehensive analysis of characteristic genes of inflammation-related bronchopulmonary dysplasia based on bioinformatics methods

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