HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma

Zeng, Zhao Chong; Huang, Huilian; Zhang, Jinming; Liu, Yuanyuan; Zhong, Wen-Fang; Chen, Weimou; Lu, Ye; Qiao, Yujie; Zhao, Haijin; Meng, Xiang‐Jin; Zou, Fei; Cai, Shaoxi; Dong, Hangming

doi:10.1096/fj.202101977rr

Cited by 43 publications

(29 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to some studies, the malfunctioning of airway epithelial cells caused by ferroptosis might be the cause of asthma control loss. In contrast, inhibiting ferroptosis might reduce inflammation associated with asthma (Wenzel et al, 2017;Zeng et al, 2022). And Wu et al ( 2020) have found that ferroptosis inducers could relieve allergic airway inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Wu et al (2020) found that the induction of ferroptosis alleviated allergic inflammation in the OVA asthma model. In contrast, Zeng et al (2022) showed that ferroptosis might occur in airway epithelial cells, and the inhibitors of ferroptosis could reduce levels of IL4, IL5, and IL13 in the HDM asthma model. Most of the currently published research on ferroptosis and asthma has focused on animal models of asthma, and only Nagasaki et al have explored the potential mechanisms of ferroptosis in asthmatics (Bao et al, 2022;Nagasaki et al, 2022).…”

Section: Introductionmentioning

confidence: 86%

See 1 more Smart Citation

Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment

Wang

Jia²,

Gu³

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Asthma was a chronic inflammatory illness driven by complicated genetic regulation and environmental exposure. The complex pathophysiology of asthma has not been fully understood. Ferroptosis was involved in inflammation and infection. However, the effect of ferroptosis on asthma was still unclear. The study was designed to identify ferroptosis-related genes in asthma, providing potential therapeutic targets.Methods: We conducted a comprehensive analysis combined with WGCNA, PPI, GO, KEGG, and CIBERSORT methods to identify ferroptosis-related genes that were associated with asthma and regulated the immune microenvironment in GSE147878 from the GEO. The results of this study were validated in GSE143303 and GSE27066, and the hub genes related to ferroptosis were further verified by immunofluorescence and RT-qPCR in the OVA asthma model.Results: 60 asthmatics and 13 healthy controls were extracted for WGCNA. We found that genes in the black module (r = −0.47, p < 0.05) and magenta module (r = 0.51, p < 0.05) were associated with asthma. CAMKK2 and CISD1 were discovered to be ferroptosis-related hub genes in the black and magenta module, separately. We found that CAMKK2 and CISD1 were mainly involved in the CAMKK-AMPK signaling cascade, the adipocytokine signaling pathway, the metal cluster binding, iron-sulfur cluster binding, and 2 iron, 2 sulfur cluster binding in the enrichment analysis, which was strongly correlated with the development of ferroptosis. We found more infiltration of M2 macrophages and less Tregs infiltration in the asthma group compared to healthy controls. In addition, the expression levels of CISD1 and Tregs were negatively correlated. Through validation, we found that CAMKK2 and CISD1 expression were upregulated in the asthma group compared to the control group and would inhibit the occurrence of ferroptosis.Conclusion: CAMKK2 and CISD1 might inhibit ferroptosis and specifically regulate asthma. Moreover, CISD1 might be tied to the immunological microenvironment. Our results could be useful to provide potential immunotherapy targets and prognostic markers for asthma.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment

Wang

Jia²,

Gu³

et al. 2023

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Fine PM triggered cytotoxicity and enhanced autophagy, oxidative stress, and the tumor necrosis factor (TNF/TNFα) pathway in human lung epithelial cells [ 64 ]. It has been reported to activate autophagy and inflammation in HBE cells in vitro and in vivo [ 65 ]. An autophagy inhibitor (3-methyladenine) suppressed PM-activated pro-inflammatory cytokine expression in vitro and in vivo in PM-treated mice [ 66 ].…”

Section: Targeting Autophagy Modulation To Eliminate Environmental Su...mentioning

confidence: 99%

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

Rahman

Parvez

et al. 2023

Toxics

View full text Add to dashboard Cite

Autophagy is an evolutionarily conserved cellular system crucial for cellular homeostasis that protects cells from a broad range of internal and extracellular stresses. Autophagy decreases metabolic load and toxicity by removing damaged cellular components. Environmental contaminants, particularly industrial substances, can influence autophagic flux by enhancing it as a protective response, preventing it, or converting its protective function into a pro-cell death mechanism. Environmental toxic materials are also notorious for their tendency to bioaccumulate and induce pathophysiological vulnerability. Many environmental pollutants have been found to influence stress which increases autophagy. Increasing autophagy was recently shown to improve stress resistance and reduce genetic damage. Moreover, suppressing autophagy or depleting its resources either increases or decreases toxicity, depending on the circumstances. The essential process of selective autophagy is utilized by mammalian cells in order to eliminate particulate matter, nanoparticles, toxic metals, and smoke exposure without inflicting damage on cytosolic components. Moreover, cigarette smoke and aging are the chief causes of chronic obstructive pulmonary disease (COPD)-emphysema; however, the disease’s molecular mechanism is poorly known. Therefore, understanding the impacts of environmental exposure via autophagy offers new approaches for risk assessment, protection, and preventative actions which will counter the harmful effects of environmental contaminants on human and animal health.

show abstract

“…[15] Treatment with ferroptosis inhibitors ferrostatin-1 (Fer-1) could alleviate airway inflammation and reduce airway epithelial cell death, indicating that airway epithelial cell ferroptosis is closely related to asthma. [16] However, in human airway epithelial cells, the genes significantly related to ferroptosis of airway epithelial cells are unknown, and whether ferroptosis genes can be used as biomarkers to discriminate normal and asthmatic patients has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics

2023

View full text Add to dashboard Cite

It has been reported that airway epithelial cells and ferroptosis have certain effect on asthma. However, the action mechanism of ferroptosis-related genes in airway epithelial cells of asthmatic patients is still unclear. Firstly, the study downloaded the GSE43696 training set, GSE63142 validation set and GSE164119 (miRNA) dataset from the gene expression omnibus database. 342 ferroptosis-related genes were downloaded from the ferroptosis database. Moreover, differentially expressed genes (DEGs) between asthma and control samples in the GSE43696 dataset were screened by differential analysis. Consensus clustering analysis was performed on asthma patients to classify clusters, and differential analysis was performed on clusters to obtain inter-cluster DEGs. Asthma-related module was screened by weighted gene co-expression network analysis. Then, DEGs between asthma and control samples, inter-cluster DEGs and asthma-related module were subjected to venn analysis for obtaining candidate genes. The last absolute shrinkage and selection operator and support vector machines were respectively applied to the candidate genes to screen for feature genes, and functional enrichment analysis was performed. Finally, a competition endogenetic RNA network was constructed and drug sensitivity analysis was conducted. There were 438 DEGs (183 up-regulated and 255 down-regulated) between asthma and control samples. 359 inter-cluster DEGs (158 up-regulated and 201 down-regulated) were obtained by screening. Then, the black module was significantly and strongly correlated with asthma. The venn analysis yielded 88 candidate genes. 9 feature genes (NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2) were screened and they were involved in proteasome, dopaminergic synapse etc. Besides, 4 mRNAs, 5 miRNAs, and 2 lncRNAs collectively formed competition endogenetic RNA regulatory network, which included RNF182-hsa-miR-455-3p-LINC00319 and so on. The predicted therapeutic drug network map contained NAV3-bisphenol A and other relationship pairs. The study investigated the potential molecular mechanisms of NAV3, ITGA10, SYT4, NOX1, SNTG2, RNF182, UPK1B, POSTN, SHISA2 in airway epithelial cells of asthmatic patients through bioinformatics analysis, providing a reference for the research of asthma and ferroptosis.

show abstract

HDM induce airway epithelial cell ferroptosis and promote inflammation by activating ferritinophagy in asthma

Cited by 43 publications

References 48 publications

Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment

Ferroptosis-related genes are involved in asthma and regulate the immune microenvironment

The Emerging Role of Autophagy as a Target of Environmental Pollutants: An Update on Mechanisms

The role of ferroptosis-related genes in airway epithelial cells of asthmatic patients based on bioinformatics

Contact Info

Product

Resources

About