Evidence map›Paper›PMID 34741186›Full record

ArticleCellular and molecular life sciences : CMLS2021

Sestrin2 protects against lethal sepsis by suppressing the pyroptosis of dendritic cells.

Li-Xue Wang, Chao Ren, Ren-Qi Yao, Yi-Nan Luo, Yue Yin, Yao Wu, Ning Dong, Xiao-Mei Zhu, Yong-Ming Yao

Open access · hybridAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
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

35 citing papers in PubMed, 52 citations in OpenAlex.

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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

9 authors at 1 institution in 1 country.

Li-Xue Wang *Chinese PLA General Hospital and Medical School of Chinese PLA, Beijing, 100853, People's Republic of China.
Chao Ren *Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing 51 Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.
Ren-Qi Yao *Translational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing 51 Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.
Yi-Nan LuoTranslational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing 51 Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.
Yue YinTranslational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing 51 Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.
Yao WuTranslational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing 51 Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.
Ning DongTranslational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing 51 Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China.
Xiao-Mei ZhuTranslational Medicine Research Center, Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital, Beijing 51 Fucheng Road, Haidian District, Beijing, 100048, People's Republic of China. yrui304@163.com.
Yong-Ming YaoChinese PLA General Hospital and Medical School of Chinese PLA, Beijing, 100853, People's Republic of China. c_ff@sina.com.ORCID http://orcid.org/0000-0002-3564-4012
Chinese PLA General Hospital · CN

Funding

National Natural Science Foundation of China 81730057National Natural Science Foundation of China 81871557National Natural Science Foundation of China 82002071the Military Medical Innovation Program of Chinese PLA 18CXZ026the Military Medical Innovation Program of Chinese PLA BLJ18J006
6 · The paper itself

Abstract

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sestrin2 (SESN2), a highly evolutionarily conserved protein, is critically involved in the cellular response to various stresses and has been confirmed to maintain the homeostasis of the internal environment. However, the potential effects of SESN2 in regulating dendritic cells (DCs) pyroptosis in the context of sepsis and the related mechanisms are poorly characterized. In this study, we found that SESN2 was capable of decreasing gasdermin D (GSDMD)-dependent pyroptosis of splenic DCs by inhibiting endoplasmic reticulum (ER) stress (ERS)-related nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated ASC pyroptosome formation and caspase-1 (CASP-1) activation. Furthermore, SESN2 deficiency induced NLRP3/ASC/CASP-1-dependent pyroptosis and the production of proinflammatory cytokines by exacerbating the PERK-ATF4-CHOP signaling pathway, resulting in an increase in the mortality of septic mice, which was reversed by inhibiting ERS. These findings suggest that SESN2 appears to be essential for inhibiting NLRP3 inflammasome hyperactivation, reducing CASP-1-dependent pyroptosis, and improving sepsis outcomes through stabilization of the ER. The present study might have important implications for exploration of novel potential therapeutic targets for the treatment of sepsis complications.

Indexed as

Protective AgentsPyroptosisAmino Acid Transport System y+AnimalsCaspase 1Dendritic CellsEndoplasmic Reticulum StressInflammasomesMaleMiceMice, Inbred C57BLMice, KnockoutNLR Family, Pyrin Domain-Containing 3 ProteinPeroxidasesSepsisSestrinsAmino Acid Transport System y+Casp1 protein, mouseCaspase 1InflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePeroxidasesProtective AgentsSesn2 protein, mouseSestrinsSlc7a10 protein, mouseDendritic cellsEndoplasmic reticulum stressInflammasomePyroptosisSepsisSestrin2

Identifiers

PMID34741186
PMCPMC8629895
OpenAlexW3208032249

What OpenQuestion 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 OpenQuestion graph.