Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 3 complete abstracts (783 words), 9 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., dna fragmentation. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Classic Apoptosis; Apoptosis, Classic; Classic Apoptoses; Classical Apoptosis; Apoptosis, Classical; Programmed Cell Death, Type I; Apoptosis, Extrinsic Pathway; Apoptoses, Extrinsic Pathway.
Where it fits in the MeSH classification
- Broader topics
- Regulated Cell Death
- Narrower topics
- Anoikis; Cuproptosis; Eryptosis; Pyroptosis
- See also
- Necrosis; Caspases; In Situ Nick-End Labeling; Cellular Apoptosis Susceptibility Protein; Genes, Transgenic, Suicide; Death Domain Receptor Signaling Adaptor Proteins; CARD Signaling Adaptor Proteins
Related concepts
Research landscape
PubMed indexes 375,422 records tagged with the MeSH heading “Apoptosis” (counts retrieved 2026-10-29). 100,581 of them (26.8%) were published from 2020 onward, and the busiest period so far is 2010-2019 with 150,018 records.
Reviews account for 34,827 records (9.3%) and meta-analyses for 139. Randomized controlled trials number 610 (0.2%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 20,068 |
| 2000-2009 | 104,755 |
| 2010-2019 | 150,018 |
| 2020 onward | 100,581 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 34,827 | 9.3% |
| Meta-analyses | 139 | 0.0% |
| Randomized controlled trials | 610 | 0.2% |
Method: PubMed query "Apoptosis"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in molecular biology
Molecular biology establishes mechanisms through controlled experiments, often in simplified systems such as purified proteins, cultured cells or model organisms. Such work can show what is possible in a defined system, but whether a pathway matters in a whole organism or in human disease needs further evidence. Check the experimental system, whether findings were reproduced by independent groups, and whether the authors tested the mechanism directly or inferred it from correlation.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 42552307 · DOI · PMC13438567 |
| Apoptosis-related genes bridge inflammatory bowel disease and osteoporosis: A bioinformatic analysis | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42585215 · DOI · PMC13465802 |
| JNK and p53 cause human and mouse β cell death during excessive unfolded protein response | 2026 | Research article Design not recorded in structured metadata | 1 | cc by PMID 42544575 · DOI · PMC13430013 |
Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Tubular epithelial cell (TEC)-macrophage crosstalk contributes to aldosterone (Aldo)-dependent renal fibrosis in hypertension.
- Closing excerpt
- Mechanism through which Aldo/MR-induced PANX1-eATP-P2X7 signaling activation promotes macrophage pyroptosis in hypertensive renal injury.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (301 words)
Tubular epithelial cell (TEC)-macrophage crosstalk contributes to aldosterone (Aldo)-dependent renal fibrosis in hypertension. Extracellular ATP (eATP) can act as a mediator of TEC-macrophage crosstalk. However, whether and how eATP functions in Aldo-induced renal injury remain unknown. A deoxycorticosterone acetate (DOCA)-salt-induced hypertensive mouse model and a primary mouse renal tubular epithelial cell (mTEC)-bone marrow-derived macrophage (BMDM) coculture model were developed. To investigate the relationship between Aldo/MR and eATP signaling in TEC-macrophage crosstalk, specific inhibitors, adeno-associated virus (AAV)-shRNA and small interfering RNA (siRNA) were used. scRNA-seq analysis of kidneys from DOCA-salt mice was performed for verification. Urinary ATP levels and renal pannexin1 (PANX1, an ATP efflux channel) expression increased significantly in DOCA-salt mice, whereas the selective mineralocorticoid receptor (MR) antagonist finerenone treatment reduced urinary ATP levels, PANX1 expression, tubular injury, and macrophage-related inflammation. Inhibiting PANX1-eATP-P2X7 signaling with the PANX1 inhibitor probenecid, specifically knocking down tubular PANX1, or using the eATP ectonucleotidase apyrase or the P2X7 blocker AZ10606120 mitigated renal tubular damage and NLRP3-mediated pyroptosis in the renal cortex of DOCA-salt mice. Similarly, in mTECs, finerenone suppressed Aldo-induced ATP release and PANX1 upregulation. A luciferase assay confirmed the binding site of MR to the PANX1 transcription promoter. Coculture of BMDMs with mTECs under Aldo stimulation significantly increased NLRP3-mediated BMDM pyroptosis and migration. However, these effects were reversed by treating the mTECs with MR or PANX1 siRNA. Similar results were observed after treatment with apyrase or AZ10606120 in the coculture system. scRNA-seq analysis further identified the activation of P2X7/NLRP3-related pyroptosis pathway in macrophages from DOCA-salt mice. In conclusion, TECs play a critical role in macrophage pyroptosis in Aldo-induced renal injury. eATP is a key messenger involved in TEC-macrophage crosstalk. PANX1-eATP-P2X7 signaling mediates TEC‒macrophage interactions to exacerbate Aldo-driven renal inflammation in hypertension. Mechanism through which Aldo/MR-induced PANX1-eATP-P2X7 signaling activation promotes macrophage pyroptosis in hypertensive renal injury.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42552307 · DOI · PMC13438567
Apoptosis-related genes bridge inflammatory bowel disease and osteoporosis: A bioinformatic analysis [2]
Abstract reading summary — source excerpts
- Opening excerpt
- BackgroundInflammatory bowel disease (IBD) and osteoporosis (OP) often co-occur, with IBD accelerating OP onset, though the underlying mechanisms remain unclear.
- Closing excerpt
- ConclusionsWNT1 and S100A8, which are associated with apoptosis, play critical roles in both inflammatory bowel disease and osteoporosis, providing new potential therapeutic targets and a theoretical basis for clinical diagnosis and treatment.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (278 words)
BackgroundInflammatory bowel disease (IBD) and osteoporosis (OP) often co-occur, with IBD accelerating OP onset, though the underlying mechanisms remain unclear.MethodsBased on gene expression data from the GEO database, differential expression analysis was performed using the limma package to identify genes dysregulated in both IBD and OP. Weighted Gene Co-expression Network Analysis (WGCNA) was employed to explore the associations between genes and phenotypes. Candidate genes were obtained by intersecting differentially expressed genes with key WGCNA modules, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. To further focus on apoptosis-related mechanisms, the candidate genes were intersected with an apoptosis-related gene set and refined using lasso regression. Core genes were identified through differential expression validation and receiver operating characteristic curve analysis. Subsequently, their potential functions and regulatory networks were explored via multidimensional analysis, gene set enrichment analysis, and Pearson correlation analysis.ResultsWNT1 and S100A8 are closely associated with the progression of both inflammatory bowel disease and osteoporosis. Gene Set Enrichment Analysis revealed that WNT1 is primarily enriched in cell cycle checkpoint signaling, chromosome organization, neuroactive ligand signaling, and neuroactive ligand-receptor interaction. In contrast, S100A8 is mainly enriched in adaptive immune response, adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily, inflammatory bowel disease, and leishmaniasis. Pearson correlation analysis showed that WNT1 is correlated with TSPAN32, POU3F3, NXPH3, EGFL7, LHX3, TNNI2, HMX1, FAM3A, IBTK, and ZNF747, while S100A8 is correlated with MMP3, SLC6A14, MMP10, S100A9, AQP9, S100A12, CXCL6, CXCR1, SLC38A4, and NCF2.ConclusionsWNT1 and S100A8, which are associated with apoptosis, play critical roles in both inflammatory bowel disease and osteoporosis, providing new potential therapeutic targets and a theoretical basis for clinical diagnosis and treatment.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42585215 · DOI · PMC13465802
JNK and p53 cause human and mouse β cell death during excessive unfolded protein response [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Endoplasmic reticulum (ER) stress contributes to β cell death in both Type 1 and Type 2 diabetes (T1D and T2D).
- Closing excerpt
- These findings provide insight into mechanisms causing β cell death during ER stress and outline possible therapeutic targets to preserve insulin secretory capacity in diabetes.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (204 words)
Endoplasmic reticulum (ER) stress contributes to β cell death in both Type 1 and Type 2 diabetes (T1D and T2D). However, the molecular mechanisms driving β cell death during ER stress remain insufficiently defined, limiting development of protective therapies. GRP78, an ER chaperone, is the master regulator of unfolded protein response (UPR), suppressing UPR initiators during the unstressed state and releasing them to allow UPR activation during stress. To dissect the pathways leading to ER-stress response related β cell decompensation, we engineered mice genetically lacking GRP78 in pancreatic β cells. GRP78 deletion caused acute insulin-deficient diabetes in pups before weaning, with reduced β cell mass due to increased apoptosis. Molecular studies identified deregulated UPR, specifically IRE1 activity, as driving cell death. Unbiased and targeted analyses identified a JNK-p53 axis downstream of IRE1 kinase as a key mediator of β cell death during UPR activation. In vivo JNK inhibition protected against β cell death in 2 distinct ER stress diabetes models. In human β cells, pharmacological inhibition of both JNK and p53 improved β cell survival during GRP78 knockdown-induced UPR. These findings provide insight into mechanisms causing β cell death during ER stress and outline possible therapeutic targets to preserve insulin secretory capacity in diabetes.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 42544575 · DOI · PMC13430013
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression [4]
- Research article Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond [5]
- Research article Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer [6]
- Research article Efferocytosis: the art of cellular clearance and novel perspectives in disease therapy [7]
- Research article Targeting ferroptosis, pyroptosis and necroptosis for cancer immunotherapy in melanoma: mechanistic insights and clinical perspectives [8]
- Research article Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances [9]
References
- Wang C, Ma H, Xu J, Tang Y, Feng J, Yang Y, et al.. Tubular epithelial cells promote macrophage pyroptosis through PANX1-extracellular ATP-P2X7 signaling in aldosterone-dependent renal injury. . 2026. PMID 42552307 · DOI · PMC13438567
- Su Y, Luo X, Xu H. Apoptosis-related genes bridge inflammatory bowel disease and osteoporosis: A bioinformatic analysis. . 2026. PMID 42585215 · DOI · PMC13465802
- Sharma RB, Darko C, Wang Y, Castro TA, Lama TD, Gablaski B, et al.. JNK and p53 cause human and mouse β cell death during excessive unfolded protein response. . 2026. PMID 42544575 · DOI · PMC13430013
- Alishvandi A, Aram C, Shahrivar FF, Kesharwani P, Sahebkar A. Pyroptosis in cancer therapy: a double-edged sword for immune activation and tumor progression. Mol Cancer. 2025. PMID 41291696 · DOI · PMC12649103
- Sendtner N, Seitz R, Brandl N, Müller M, Gülow K. Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond. Int J Mol Sci. 2025. PMID 41155529 · DOI · PMC12564638
- Hao Q, Gan Y, Zhou X. Tackling cuproptosis: from metabolic rewiring to therapeutic exploitation in cancer. Cell Mol Immunol. 2026. PMID 41588247 · DOI · PMC12949048
- Li G, Xu J, Tian X, Xiao J, Long J, Chen Y, et al.. Efferocytosis: the art of cellular clearance and novel perspectives in disease therapy. Mol Cancer. 2025. PMID 41126210 · DOI · PMC12548151
- Shan Z, Liu F. Targeting ferroptosis, pyroptosis and necroptosis for cancer immunotherapy in melanoma: mechanistic insights and clinical perspectives. Front Immunol. 2025. PMID 41235238 · DOI · PMC12605190
- Seo W, Jung B, Roh T, Shin HJ, Song IC, Chung C, et al.. Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances. J Hematol Oncol. 2025. PMID 41291897 · DOI · PMC12751675
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.