ArticlePLoS genetics2022
Blocking Caspase-1/Gsdmd and Caspase-3/-8/Gsdme pyroptotic pathways rescues silicosis in mice.
Article in PLoS genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Fumarate and Its Esters: Physiology, Pathology, Molecular Mechanisms, Diseases, and Therapy.MedComm · 2026Review
- Targeting the non-coding RNA-PANoptosis axis: a novel frontier in disease diagnosis and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Monosodium urate crystals induce lytic macrophage death partially dependent on both pyroptosis and necroptosis.Clinical rheumatology · 2026Article
- PAD4-generated citrullinated histones are triggers for autoinflammation in cryopyrin-associated periodic syndrome.Cell death and differentiation · 2026Article
- The challenge of cell death switching in inflammasome-targeted therapies for bacterial and viral infections.Communications biology · 2026Review
- Article
- Targeting pyroptosis in renal fibrosis: From molecular mechanisms to therapeutic horizons (Review).International journal of molecular medicine · 2026Review
- Lymphocyte homing disorder: a concealed driver of intestinal immune collapse in sepsis.Frontiers in immunology · 2026Review
- Targeting Programmed Cell Death in Depression: A Review of Traditional Chinese Medicine Interventions Based on Preclinical Evidence.Neuropsychiatric disease and treatment · 2026Review
- Dimethyl fumarate ameliorated pyroptosis in contrast-induced acute renal injury by regulating endoplasmic reticulum stress and JAK2-STAT3 pathway.Renal failure · 2025Article
- Article
- NLRP3 deficiency abrogates silica-induced neutrophil infiltration, pulmonary damage and fibrosis.Respiratory research · 2025Article
- The EMCV protein 2B* is required for efficient cell lysis via both caspase-3-dependent and -independent pathways during infection.The Journal of general virology · 2025Article
- The role of NLRP3 inflammasome-mediated pyroptosis in astrocytes during hyperoxia-induced brain injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- GSDME in cardiovascular diseases: research system and contemporary progress.Frontiers in immunology · 2025Review
- Inhibition of Caspase-3/GSDME Pathway-Mediated Pyroptosis of Renal Tubular Epithelial Cells by Dagliflozin in the Pathogenesis of Diabetic Kidney Disease and Study of Its Mechanism.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Inhibition of NLRP3 inflammasome contributes to paclitaxel efficacy in triple negative breast cancer treatment.Scientific reports · 2024Article
- Gasdermin D and Gasdermin E Are Dispensable for Silica-Mediated IL-1β Secretion from Mouse Macrophages.ImmunoHorizons · 2024Article
- The role of pyroptosis in the occurrence and development of pregnancy-related diseases.Frontiers in immunology · 2024Review
- A comprehensive retrospect on the current perspectives and future prospects of pneumoconiosis.Frontiers in public health · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Millions of patients suffer from silicosis, but it remains an uncurable disease due to its unclear pathogenic mechanisms. Though the Nlrp3 inflammasome is involved in silicosis pathogenesis, inhibition of its classic downstream factors, Caspase-1 and Gsdmd, fails to block pyroptosis and cytokine release. To clarify the molecular mechanism of silicosis pathogenesis for new therapy, we examined samples from silicosis patients and genetic mouse models. We discovered an alternative pyroptotic pathway which requires cleavage of Gsdme by Caspases-3/8 in addition to Caspase-1/Gsdmd. Consistently, Gsdmd-/-Gsdme-/- mice showed markedly attenuated silicosis pathology, and Gsdmd-/-Gsdme-/- macrophages were resistant to silica-induced pyroptosis. Furthermore, we found that in addition to Caspase 1, Caspase-8 cleaved IL-1β in silicosis, explaining why Caspase-1-/- mice also suffered from silicosis. Finally, we found that inhibitors of Caspase-1, -3, -8 or an FDA approved drug, dimethyl fumarate, could dramatically alleviate silicosis pathology through blocking cleavage of Gsdmd and Gsdme. This study highlights that Caspase-1/Gsdmd and Caspase-3/8/Gsdme-dependent pyroptosis is essential for the development of silicosis, implicating new potential targets and drug for silicosis treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.