Evidence map›Paper›PMID 39349939›Full record

ArticleCell death & disease2024

Ubiquitin-independent degradation of Bim blocks macrophage pyroptosis in sepsis-related tissue injury.

Peilin Shi, Yingying Du, Yunyan Zhang, Bo Yang, Qiujing Guan, Yiming Jing, Hao Tang, Jianguo Tang, Chunhui Yang, Xiaoli Ge and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Peilin Shi *Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai, 200241, China.
Yingying Du *Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai, 200241, China.
Yunyan Zhang *Department of Respiratory and Critical Care Medicine, Changzheng Hospital, Naval Military Medical University, Shanghai, 200003, China.
Bo YangShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai, 200241, China.
Qiujing GuanShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai, 200241, China.
Yiming JingShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences, East China Normal University, Shanghai, 200241, China.
Hao TangDepartment of Respiratory and Critical Care Medicine, Changzheng Hospital, Naval Military Medical University, Shanghai, 200003, China.
Jianguo TangJoint Center for Translational Medicine, Shanghai Fifth People's Hospital, Fudan University and School of Life Science, East China Normal University, Shanghai, 200011, China.
Chunhui YangJoint Center for Translational Medicine, Shanghai Fifth People's Hospital, Fudan University and School of Life Science, East China Normal University, Shanghai, 200011, China.
Xiaoli GeDepartment of Emergency, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
Shihui ShenJoint Center for Translational Medicine, Shanghai Fifth People's Hospital, Fudan University and School of Life Science, East China Normal University, Shanghai, 200011, China. shshen@bio.ecnu.edu.cn.
Lei LiJoint Center for Translational Medicine, Shanghai Fifth People's Hospital, Fudan University and School of Life Science, East China Normal University, Shanghai, 200011, China. lli@bio.ecnu.edu.cn.ORCID 0000-0002-3114-1653
Chunrong WuJoint Center for Translational Medicine, Shanghai Fifth People's Hospital, Fudan University and School of Life Science, East China Normal University, Shanghai, 200011, China. wuchunrong@5thhospital.com.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81971861National Natural Science Foundation of China (National Science Foundation of China) 82022051, 82372456National Natural Science Foundation of China (National Science Foundation of China) 82022051,82372456Science and Technology Commission of Shanghai Municipality (Shanghai Municipal Science and Technology Commission) 20S11901500
6 · The paper itself

Abstract

Pyroptosis, a typical inflammatory cell death mode, has been increasingly demonstrated to have therapeutic value in inflammatory diseases such as sepsis. However, the mechanisms and therapeutic targets of sepsis remain elusive. Here, we reported that REGγ inhibition promoted pyroptosis by regulating members of the gasdermin family in macrophages. Mechanistically, REGγ directly degraded Bim, a factor of the Bcl-2 family that can inhibit the cleavage of GSDMD/E, ultimately preventing the occurrence of pyroptosis. Furthermore, cecal ligation and puncture (CLP)-induced sepsis model mice showed downregulation of REGγ at both the RNA and protein levels. Gasdermin-mediated pyroptosis was augmented in REGγ-knockout mice, and these mice exhibited more severe sepsis-related tissue injury. More importantly, we found that REGγ expression was downregulated in clinical sepsis samples, such as those from patients with Pseudomonas aeruginosa (PA) infection. Finally, PA-infected mice showed decreased REGγ levels in the lung. In summary, our study reveals that the REGγ-Bim-GSDMD/E pathway is a novel regulatory mechanism of pyroptosis in sepsis-related tissue injury.

Indexed as

Bcl-2-Like Protein 11MacrophagesMice, KnockoutPyroptosisSepsisAnimalsAutoantigensDisease Models, AnimalGasderminsHumansIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLPhosphate-Binding ProteinsPore Forming Cytotoxic ProteinsAutoantigensBcl-2-Like Protein 11GasderminsGsdmd protein, mouseGsdme protein, mouseIntracellular Signaling Peptides and ProteinsKi antigenPhosphate-Binding ProteinsPore Forming Cytotoxic ProteinsProteasome Endopeptidase ComplexUbiquitin

Identifiers

PMID39349939
PMCPMC11442472

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.