ArticleJCI insight2021
RIP3-dependent necroptosis contributes to the pathogenesis of chronic obstructive pulmonary disease.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 64 citations in OpenAlex.
- MLKL regulates intracellular trafficking of neutrophil elastase to promote lung epithelial cell senescence.American journal of respiratory cell and molecular biology · 2026Article
- Attenuated FTO induces necroptosis of alveolar epithelium via the mRedox biology · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- Necroptosis in alveolar epithelium orchestrates lung ischemia-reperfusion injury: a multi-omics study.Respiratory research · 2026Article
- In mice, a population of male germ cells show characteristics of non-apoptotic cell death during G0 arrest.bioRxiv : the preprint server for biology · 2026Article
- Targeting phenol-soluble modulin α3-driven M1 macrophage polarization and necroptosis mitigates MRSA infection in mice.Nature communications · 2026Article
- Advances in research on hyperoxia-induced acute lung injury: from pathogenesis to therapy.Frontiers in cell and developmental biology · 2026Review
- NOD1 modulates chronic obstructive pulmonary disease progression via FOXA1/NLRP3-mediated regulation of pyroptosis.Frontiers in immunology · 2026Article
- Focus on necroptosis: its role in the pathogenesis and therapeutic potential of osteoarthritis.Frontiers in immunology · 2026Review
- The role of programmed cell death in chronic obstructive pulmonary disease: from pathogenesis to treatment.Frontiers in immunology · 2026Review
- Review
- Review
- Life-threatening risk factors contribute to the development of diseases with the highest mortality through the induction of regulated necrotic cell death.Cell death & disease · 2025Review
- The Multifaceted Roles of Neutrophil Death in COPD and Lung Cancer.Journal of respiratory biology and translational medicine · 2025Article
- Lung organoids in COPD: recent advances and future prospects.Respiratory research · 2025Review
- [Prospects of Smoking Hazards Research Using Lung Organoid].Jugan geon-gang gwa jilbyeong · 2025Review
- Cigarette smoke exposure triggers dendritic cell-derived exosome-mediated Th17 and Treg polarization through an autophagy- and necroptosis-associated SIRT1-dependent mechanism in vitro.Frontiers in immunology · 2025Article
- Lipolysis engages CD36 to promote ZBP1-mediated necroptosis-impairing lung regeneration in COPD.Cell reports. Medicine · 2024Article
- Targeting necroptosis: a promising avenue for respiratory disease treatment.Cell communication and signaling : CCS · 2024Review
- HIST3H2A promotes the progression of prostate cancer through inhibiting cell necroptosis.BMC cancer · 2024Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Necroptosis has emerged as a potential mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we found that markers of necroptosis, including high mobility group box 1 release and phosphorylation of mixed lineage kinase domain-like protein (p-MLKL), were markedly induced in the late stage of cigarette smoking-induced (CS-induced) emphysema in mouse lung tissue as well as in lung epithelial cells and organoids with higher dosage of or more prolonged exposure to cigarette smoking extract (CSE). Apoptotic signals were also detected and maximally induced in the early stage of CS-exposed mice and CSE-treated epithelial cells. Inhibition of apoptosis by Z-VAD, a pan-caspase inhibitor, switched the cellular stress to enhanced necroptosis in lung epithelial cells and organoids treated with CSE. Depletion or inhibition of receptor-interacting protein kinase 3 (RIP3) or MLKL attenuated the CSE-induced cell death, suggesting that necroptosis contributes to CSE-induced cell death. Silencing or inhibition of RIP1 had no protective effect, indicating a RIP1-independent RIP3 activation pathway. CSE-induced necroptosis released more damage-associated molecular patterns and evoked greater engulfment but slower clearance by bone marrow-derived macrophages, leading to enhanced expression of proinflammatory cytokines Tnfα and Il6. Finally, our in vivo data verified that inhibition of necroptosis by RIP3 inhibitor GSK'872 protected mice from CS-induced emphysema and suppressed the lung inflammation. In conclusion, we provide evidence that necroptosis contributes to the pathogenesis of COPD. Targeting RIP3 and its downstream pathway may be an effective therapy for COPD.
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