The role of ferroptosis in chronic intermittent hypoxia-induced lung injury

Chen, Jia; Zhu, Hongtao; Chen, Qin; Yang, Yisong; Chen, Mengxue; Huang, Jiefeng; Chen, Menglan; Lian, Ningfang

doi:10.1186/s12890-022-02262-x

Cited by 10 publications

(3 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Chronic intermittent hypoxia is the main clinical feature of OSA patients. Chen et al ( 39 ) reported chronic intermittent hypoxia induced intracellular ROS accumulation, which leads to ferroptosis. Simultaneously, DEmRNAs-enriched signaling pathways (such as Wnt signaling pathway, MAPK signaling pathway, and Calcium signaling pathway) are also involved in the regulation of ferroptosis ( 23 , 40 , 41 ), so we speculated that ferroptosis-related genes are the molecular targets of CPAP treatment of OSA.…”

Section: Discussionmentioning

confidence: 99%

Ferroptosis-related genes are considered as potential targets for CPAP treatment of obstructive sleep apnea

Huang,

Zhang,

Cao

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

Obstructive sleep apnea (OSA) is a common syndrome characterized by upper airway dysfunction during sleep. Continuous positive airway pressure (CPAP) is the most frequently utilized non-surgical treatment for OSA. Ferroptosis play a crucial role in the physiological diseases caused by chronic intermittent hypoxia, but its involvement in the development of OSA and the exact mechanisms have incompletely elucidated. GSE75097 microarray dataset was used to identify differentially expressed genes between OSA patients and CPAP-treated OSA patients. Subsequently, Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, STRING database, and FerrDb database were conducted to analyze the biological functions of differentially expressed genes and screen ferroptosis-related genes. Finally, GSE135917 dataset employed for validation. There were 1,540 differentially expressed genes between OSA patients and CPAP-treated OSA patients. These differentially expressed genes were significantly enriched in the regulation of interleukin-1-mediated signaling pathway and ferroptosis-related signaling pathway. Subsequently, 13 ferroptosis-related genes (DRD5, TSC22D3, TFAP2A, STMN1, DDIT3, MYCN, ELAVL1, JUN, DUSP1, MIB1, PSAT1, LCE2C, and MIR27A) were identified from the interaction between differentially expressed genes and FerrDb database, which are regarded as the potential targets of CPAP-treated OSA. These ferroptosis-related genes were mainly involved in cell proliferation and apoptosis and MAPK signaling pathway. Furthermore, DRD5 and TFAP2A were downregulated in OSA patients, which showed good diagnostic properties for OSA, but these abnormal signatures are not reversed with short-term effective CPAP therapy. In summary, the identification of 13 ferroptosis-related genes as potential targets for the CPAP treatment of OSA provides valuable insights into the development of novel, reliable, and accurate therapeutic options.

show abstract

Section: Discussionmentioning

confidence: 99%

Ferroptosis-related genes are considered as potential targets for CPAP treatment of obstructive sleep apnea

Huang,

Zhang,

Cao

et al. 2023

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…Of note, Fer-1 is a widely utilized small molecule inhibitor of ferroptosis in laboratory settings. It has been reported to upregulate GPX4 expression and impede the progression of PF [166][167][168]. However, its unfavorable pharmacokinetic profile renders it unsuitable for clinical application [20].…”

Section: Clearance Of Lipid Peroxidesmentioning

confidence: 99%

Emerging roles of ferroptosis in pulmonary fibrosis: current perspectives, opportunities and challenges

Hu,

Huang,

Zong

et al. 2024

Cell Death Discov.

View full text Add to dashboard Cite

Pulmonary fibrosis (PF) is a chronic interstitial lung disorder characterized by abnormal myofibroblast activation, accumulation of extracellular matrix (ECM), and thickening of fibrotic alveolar walls, resulting in deteriorated lung function. PF is initiated by dysregulated wound healing processes triggered by factors such as excessive inflammation, oxidative stress, and coronavirus disease (COVID-19). Despite advancements in understanding the disease’s pathogenesis, effective preventive and therapeutic interventions are currently lacking. Ferroptosis, an iron-dependent regulated cell death (RCD) mechanism involving lipid peroxidation and glutathione (GSH) depletion, exhibits unique features distinct from other RCD forms (e.g., apoptosis, necrosis, and pyroptosis). Imbalance between reactive oxygen species (ROS) production and detoxification leads to ferroptosis, causing cellular dysfunction through lipid peroxidation, protein modifications, and DNA damage. Emerging evidence points to the crucial role of ferroptosis in PF progression, driving macrophage polarization, fibroblast proliferation, and ECM deposition, ultimately contributing to alveolar cell death and lung tissue scarring. This review provides a comprehensive overview of the latest findings on the involvement and signaling mechanisms of ferroptosis in PF pathogenesis, emphasizing potential novel anti-fibrotic therapeutic approaches targeting ferroptosis for PF management.

show abstract

“…Ferroptosis can also be induced in normal cells under hypoxia conditions. It was reported that chronic intermittent hypoxia (CIH) induced ferroptosis in the hippocampus, lung, liver, and cardiomyocytes by downregulating NRF2 and GPX4, as well as upregulating ACSL4, leading to cognitive impairment and injury of brain, lung liver, and heart [ 122 , 123 , 124 , 125 ]. In the brain, hypoxic-ischemic induces ferroptosis with the increased TFRC expression, and decreased expression of SLC7A11, TRX-1, and GPX4 [ 126 , 127 , 128 ].…”

Section: The Mechanism and Regulation Of Ferroptosis Modulated By Hyp...mentioning

confidence: 99%

Ferroptosis Regulated by Hypoxia in Cells

Zheng

Liang

Zhang

2023

Cells

View full text Add to dashboard Cite

Ferroptosis is an oxidative damage-related, iron-dependent regulated cell death with intracellular lipid peroxide accumulation, which is associated with many physiological and pathological processes. It exhibits unique features that are morphologically, biochemically, and immunologically distinct from other regulated cell death forms. Ferroptosis is regulated by iron metabolism, lipid metabolism, anti-oxidant defense systems, as well as various signal pathways. Hypoxia, which is found in a group of physiological and pathological conditions, can affect multiple cellular functions by activation of the hypoxia-inducible factor (HIF) signaling and other mechanisms. Emerging evidence demonstrated that hypoxia regulates ferroptosis in certain cell types and conditions. In this review, we summarize the basic mechanisms and regulations of ferroptosis and hypoxia, as well as the regulation of ferroptosis by hypoxia in physiological and pathological conditions, which may contribute to the numerous diseases therapies.

show abstract

The role of ferroptosis in chronic intermittent hypoxia-induced lung injury

Cited by 10 publications

References 39 publications

Ferroptosis-related genes are considered as potential targets for CPAP treatment of obstructive sleep apnea

Ferroptosis-related genes are considered as potential targets for CPAP treatment of obstructive sleep apnea

Emerging roles of ferroptosis in pulmonary fibrosis: current perspectives, opportunities and challenges

Ferroptosis Regulated by Hypoxia in Cells

Contact Info

Product

Resources

About