Evidence map›Paper›PMID 34743181›Full record

ArticleCell death discovery2021

LPS-induced macrophage HMGB1-loaded extracellular vesicles trigger hepatocyte pyroptosis by activating the NLRP3 inflammasome.

Guozhen Wang, Siyi Jin, Weichang Huang, Yang Li, Jun Wang, Xuguang Ling, Yun Huang, Ye Hu, Congcong Li, Ying Meng and 1 more

Open access · goldAbstract read
In one paragraph

Article in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.

0numbers the graph read from it
0cells of the map it votes in
76citing papers in PubMed
5.9field-weighted citation impact, top 2% 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

76 citing papers in PubMed, 106 citations in OpenAlex.

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  6. IGF2BP1 modulates ZDHHC5-mediated NLRP3 inflammasome activation to promote mitochondrial damage and foam cell formation of vascular smooth muscle cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  7. Targeting FAPActa pharmaceutica Sinica. B · 2026
    Article
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16 more citing papers are in PubMed but not listed here.

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

11 authors at 1 institution in 1 country.

Guozhen Wang *Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
Siyi Jin *State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China.
Weichang Huang *Department of Emergency Medicine, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
Yang LiState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China.
Jun WangState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China.
Xuguang LingDepartment of Emergency Medicine, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China.
Yun HuangState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China.
Ye HuState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China.
Congcong LiState Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, Guangdong, China.
Ying MengDepartment of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China. nfyymengy@163.com.ORCID http://orcid.org/0000-0001-8865-652X
Xu LiDepartment of Emergency Medicine, Nanfang Hospital, Southern Medical University, 510515, Guangzhou, China. mylx99@smu.edu.cn.ORCID http://orcid.org/0000-0002-0765-5494
Nanfang Hospital · CN

Funding

China Postdoctoral Science Foundation No. F119NF0124National Natural Science Foundation of China (National Science Foundation of China) No. 81670556National Natural Science Foundation of China (National Science Foundation of China) No. 81900581
6 · The paper itself

Abstract

Extracellular vesicles (EVs) have emerged as important vectors of intercellular dialogue. High mobility group box protein 1 (HMGB1) is a typical damage-associated molecular pattern (DAMP) molecule, which is cytotoxic and leads to cell death and tissue injury. Whether EVs are involved in the release of HMGB1 in lipopolysaccharide (LPS)-induced acute liver injuries need more investigation. EVs were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blotting. The co-localization of HMGB1, RAGE (receptor for advanced glycation end-products), EEA1, Rab5, Rab7, Lamp1 and transferrin were detected by confocal microscopy. The interaction of HMGB1 and RAGE were investigated by co-immunoprecipitation. EVs were labeled with the PKH67 and used for uptake experiments. The pyroptotic cell death was determined by FLICA 660-YVAD-FMK. The expression of NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasomes were analyzed by western-blot or immunohistochemistry. Serum HMGB1, ALT (alanine aminotransferase), AST (aspartate aminotransferase), LDH (lactate dehydrogenase) and MPO (myeloperoxidase) were measured using a commercial kit. The extracellular vesicle HMGB1 was detected in the serums of sepsis patients. Macrophages were found to contribute to HMGB1 release through the EVs. HMGB1-RAGE interactions participated in the loading of HMGB1 into the EVs. These EVs shuttled HMGB1 to target cells by transferrin-mediated endocytosis leading to hepatocyte pyroptosis by the activation of NLRP3 inflammasomes. Moreover, a positive correlation was verified between the sepsis serum EVs-HMGB1 level and clinical liver damage. This finding provides insights for the development of novel diagnostic and therapeutic strategies for acute liver injuries.

Identifiers

PMID34743181
PMCPMC8572226
OpenAlexW3211703389

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Registered trials

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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.