TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in allergic airway inflammation

Sha, Jia-Feng; Xie, Qiu-Meng; Chen, Ning; Song, Si-Ming; Ruan, Ya; Zhao, Cui-Cui; Liu, Qian; Shi, Ronghua; Jiang, Xuqin; Zhang, Xu; Wu, Hui-Mei

doi:10.1016/j.freeradbiomed.2023.03.007

Cited by 4 publications

(3 citation statements)

References 53 publications

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“…miRNA‐18a inhibits HIF1‐α/NLRP3 signalling to hinder pyroptosis and impair osteogenic differentiation 51 . HIF‐1α‐mediated glycolysis deficiency also alleviates NLRP3‐related inflammation, pyroptosis and oxidative stress 52 . These reports revealed that HIF‐1α interacts with specific proteins, signalling pathways and genetic regulators to promote cell death processes, especially NLRP3 signalling‐dependent pyroptosis.…”

Section: Discussionmentioning

confidence: 96%

“… 51 HIF‐1α‐mediated glycolysis deficiency also alleviates NLRP3‐related inflammation, pyroptosis and oxidative stress. 52 These reports revealed that HIF‐1α interacts with specific proteins, signalling pathways and genetic regulators to promote cell death processes, especially NLRP3 signalling‐dependent pyroptosis. Whether and how other forms of cell death, such as apoptosis, necrotic apoptosis and ferroptosis, are induced by energy metabolism alterations and mitochondrial dysfunction‐mediated ROS production under hypoxia in PHG and GC tissues warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

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Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Xiao,

Liu,

Xie

et al. 2024

Clinical & Translational Med

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IntroductionHypoxia is an important characteristic of gastric mucosal diseases, and hypoxia‐inducible factor‐1α (HIF‐1α) contributes to microenvironment disturbance and metabolic spectrum abnormalities. However, the underlying mechanism of HIF‐1α and its association with mitochondrial dysfunction in gastric mucosal lesions under hypoxia have not been fully clarified.ObjectivesTo evaluate the effects of hypoxia‐induced HIF‐1α on the development of gastric mucosal lesions.MethodsPortal hypertensive gastropathy (PHG) and gastric cancer (GC) were selected as representative diseases of benign and malignant gastric lesions, respectively. Gastric tissues from patients diagnosed with the above diseases were collected. Portal hypertension (PHT)‐induced mouse models in METTL3 mutant or NLRP3‐deficient littermates were established, and nude mouse gastric graft tumour models with relevant inhibitors were generated. The mechanisms underlying hypoxic condition, mitochondrial dysfunction and metabolic alterations in gastric mucosal lesions were further analysed.ResultsHIF‐1α, which can mediate mitochondrial dysfunction via upregulation of METTL3/IGF2BP3‐dependent dynamin‐related protein 1 (Drp1) N6‐methyladenosine modification to increase mitochondrial reactive oxygen species (mtROS) production, was elevated under hypoxic conditions in human and mouse portal hypertensive gastric mucosa and GC tissues. While blocking HIF‐1α with PX‐478, inhibiting Drp1‐dependent mitochondrial fission via mitochondrial division inhibitor 1 (Mdivi‐1) treatment or METTL3 mutation alleviated this process. Furthermore, HIF‐1α influenced energy metabolism by enhancing glycolysis via lactate dehydrogenase A. In addition, HIF‐1α‐induced Drp1‐dependent mitochondrial fission also enhanced glycolysis. Drp1‐dependent mitochondrial fission and enhanced glycolysis were associated with alterations in antioxidant enzyme activity and dysfunction of the mitochondrial electron transport chain, resulting in massive mtROS production, which was needed for activation of NLRP3 inflammasome to aggravate the development of the PHG and GC.ConclusionsUnder hypoxic conditions, HIF‐1α enhances mitochondrial dysfunction via Drp1‐dependent mitochondrial fission and influences the metabolic profile by altering glycolysis to increase mtROS production, which can trigger NLRP3 inflammasome activation and mucosal microenvironment alterations to contribute to the development of benign and malignant gastric mucosal lesions.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Xiao,

Liu,

Xie

et al. 2024

Clinical & Translational Med

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show abstract

“…OVA-induced acute allergic airway inflammation model was established as reported in our previous study [ 41 , 42 ]. On days 0 and 7, mice were sensitized with 0.5 mL suspension consisting of 10 μg OVA (Sigma-Aldrich, St. Louis, MO, USA) and 1 mg KAl (SO4) 2 (Sangon Biotech, Shanghai, China) in saline intraperitoneally.…”

Section: Methodsmentioning

confidence: 99%

Melatonin regulates circadian clock proteins expression in allergic airway inflammation

Guo,

Jiang,

Chen

et al. 2024

Heliyon

Self Cite

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Dexamethasone protects against asthma via regulating Hif-1α-glycolysis-lactate axis and protein lactylation

Chen,

Xie,

Song

et al. 2024

International Immunopharmacology

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TLR2-hif1α-mediated glycolysis contributes to pyroptosis and oxidative stress in allergic airway inflammation

Cited by 4 publications

References 53 publications

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Mitochondrial dysfunction induced by HIF‐1α under hypoxia contributes to the development of gastric mucosal lesions

Melatonin regulates circadian clock proteins expression in allergic airway inflammation

Dexamethasone protects against asthma via regulating Hif-1α-glycolysis-lactate axis and protein lactylation

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