Evidence map›Paper›PMID 39604886›Full record

ArticleRespiratory research2024

Inhibition of IRE1α/XBP1 axis alleviates LPS-induced acute lung injury by suppressing TXNIP/NLRP3 inflammasome activation and ERK/p65 signaling pathway.

Sijiao Wang, Lijuan Hu, Yipeng Fu, Fan Xu, Yue Shen, Hanhan Liu, Lei Zhu

Abstract read
In one paragraph

Article in Respiratory research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
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  3. Cells · 2026
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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

7 authors.

Sijiao Wang *Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Lijuan Hu *Department of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Yipeng Fu *Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200011, China.
Fan XuDepartment of Intensive Care Unit, Peoples Hospital of Peking University, Beijing, 100044, China.
Yue ShenDepartment of Respiratory and Critical Care Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, P.R. China.
Hanhan LiuDepartment of Respiratory and Critical Care Medicine, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, China. lhhssym@163.com.
Lei ZhuDepartment of Respiratory and Critical Care Medicine, Department of Respiratory and Critical Care Medicine, Huadong Hospital, Fudan University, Shanghai, 200040, China. tfzhu@126.com.

Funding

National Natural Science Foundation of China 82070075Shanghai Municipal Health Commission 20214Y0389
6 · The paper itself

Abstract

backgroundAcute lung injury or acute respiratory distress syndrome (ALI/ARDS) is a devastating clinical syndrome with high incidence and mortality rates. IRE1α-XBP1 pathway is one of the three major signaling axes of endoplasmic reticulum stress that is involved in inflammation, metabolism, and immunity. The role and potential mechanisms of IRE1α-XBP1 axis in ALI/ARDS has not well understood.

methodsThe ALI murine model was established by intratracheal administration of lipopolysaccharide (LPS). Hematoxylin and eosin (H&E) staining and analysis of bronchoalveolar lavage fluid (BALF) were used to evaluate degree of lung injury. Inflammatory responses were assessed by ELISA and RT-PCR. Apoptosis was evaluated using TUNEL staining and western blot. Moreover, western blot, immunohistochemistry, and immunofluorescence were applied to test expression of IRE1α, XBP1, NLRP3, TXNIP, IL-1β, ERK1/2 and NF-κB p65.

resultsThe expression of IRE1α significantly increased after 24 h of LPS treatment. Inhibition of the IRE1α-XBP1 axis with 4µ8C notably improved LPS-induced lung injury and inflammatory infiltration, reduced the levels of IL-6, IL-1β, and TNF-α, and decreased cell apoptosis as well as the activation of the NLRP3 inflammasome. Besides, in LPS-stimulated Beas-2B cells, both 4µ8C and knockdown of XBP1 diminished the mRNA levels of IL-6 and IL-1B, inhibited cell apoptosis and reduced the protein levels of TXNIP, NLRP3 and secreted IL-1β. Mechanically, the phosphorylation and nuclear translocation of ERK1/2 and p65 were significantly suppressed by 4µ8C and XBP1 knockdown.

conclusionsIn summary, our findings suggest that IRE1α-XBP1 axis is crucial in the pathogenesis of ALI/ARDS, whose suppression could mitigate the pulmonary inflammatory response and cell apoptosis in ALI through the TXNIP/NLRP3 inflammasome and ERK/p65 signaling pathway. Our study may provide new evidence that IRE1α-XBP1 may be a promising therapeutic target for ALI/ARDS.

Indexed as

Acute Lung InjuryCarrier ProteinsEndoribonucleasesInflammasomesLipopolysaccharidesMice, Inbred C57BLNLR Family, Pyrin Domain-Containing 3 ProteinProtein Serine-Threonine KinasesTranscription Factor RelAX-Box Binding Protein 1AnimalsMaleMAP Kinase Signaling SystemMiceSignal TransductionThioredoxinsCarrier ProteinsEndoribonucleasesErn1 protein, mouseInflammasomesLipopolysaccharidesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseProtein Serine-Threonine KinasesRela protein, mouseThioredoxinsTranscription Factor RelATxnip protein, mouseX-Box Binding Protein 1Xbp1 protein, mouseAcute lung injuryERK/p65InflammationIRE1α-XBP1 axisNRLP3

Identifiers

PMID39604886
PMCPMC11603636

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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.