Evidence mapPaperPMID 40045003Full record

ArticleCell biology and toxicology2025

Neutrophil-derived heparin-binding protein increases endothelial permeability in acute lung injury by promoting TRIM21 and the ubiquitination of P65.

Jian Zhang, Yong Cao, Wenqi Shu, Senxiao Dong, Yini Sun, Xiaochun Ma

Abstract read
In one paragraph

Article in Cell biology and toxicology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Review
  2. Review
  3. [Association between heparin-binding protein and other clinical indicators with the microscopic severity ofZhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2026
    Article
  4. Article
  5. Article
  6. 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

6 authors.

Jian ZhangDepartment of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China.
Yong CaoDepartment of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China.
Wenqi ShuDepartment of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China.
Senxiao DongDepartment of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China.
Yini SunDepartment of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China.
Xiaochun MaDepartment of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang, 110001, Liaoning Province, People's Republic of China. maxc_cmu@sina.com.

Funding

Nature and Science Foundation of China 82172130
6 · The paper itself

Abstract

Acute lung injury (ALI), which poses a significant public health threat, is commonly caused by sepsis. ALI is associated with permeability and glycolysis changes in pulmonary microvascular endothelial cells. Our study demonstrates that heparin-binding protein (HBP), released from neutrophils during sepsis, exacerbates endothelial permeability and glycolysis, thereby triggering ALI. Through coimmunoprecipitation and mass spectrometry, TRIM21 was identified as a HBP interaction partner. Notably, HBP enhances the protein stability of TRIM21 by inhibiting K48 ubiquitination. TRIM21 binds to and promotes K63-linked ubiquitination of P65, facilitating its nuclear translocation. TRIM21 regulates HPMEC permeability and glycolysis in a manner dependent on P65 nuclear translocation. HBP stabilizes TRIM21 and enhances TRIM21 interactions with P65. Rescue experiments conducted in vivo and in vitro demonstrate that modulation of endothelial permeability and glycolysis by HBP is predominantly mediated through the TRIM21-P65 axis. Our results suggest that targeting the HBP/TRIM21/P65 axis is a novel therapeutic strategy to ameliorate ALI.

Indexed as

Acute Lung InjuryEndothelial CellsNeutrophilsRibonucleoproteinsTranscription Factor RelAAnimalsCapillary PermeabilityGlycolysisHumansMaleMiceMice, Inbred C57BLPermeabilitySS-A AntigenUbiquitinationRibonucleoproteinsSS-A AntigenTranscription Factor RelAAcute lung injuryHeparin-binding proteinP65TRIM21Ubiquitination

Identifiers

PMID40045003
PMCPMC11882632

What Socratic holds

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LicenceCC BY-NC-ND
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.