Evidence map›Paper›PMID 37810232›Full record

ArticleiScience2023

The senescent secretome drives PLVAP expression in cultured human hepatic endothelial cells to promote monocyte transmigration.

Alex L Wilkinson, Samuel Hulme, James I Kennedy, Emily R Mann, Paul Horn, Emma L Shepherd, Kelvin Yin, Marco Y W Zaki, Gareth Hardisty, Wei-Yu Lu and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in iScience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.8field-weighted citation impact, top 24% 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

5 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Review
  5. 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

16 authors at 7 institutions in 3 countries.

Alex L WilkinsonCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Samuel HulmeCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
James I KennedyCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Emily R MannCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Paul HornCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Emma L ShepherdCollege of Health and Life Sciences, Aston University, Birmingham B4 7ET, UK.
Kelvin YinUniversity of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK.
Marco Y W ZakiDepartment of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
Gareth HardistyCentre for Inflammation Research, University of Edinburgh, Edinburgh EH8 9YL, UK.
Wei-Yu LuCentre for Inflammation Research, University of Edinburgh, Edinburgh EH8 9YL, UK.
Pia RantakariInstitute of Biomedicine, University of Turku, Turku, Finland.
David H AdamsCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Marko SalmiInstitute of Biomedicine, University of Turku, Turku, Finland.
Matthew HoareUniversity of Cambridge, Cancer Research UK Cambridge Institute, Robinson Way, Cambridge CB2 0RE, UK.
Daniel A PattenCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
Shishir ShettyCentre for Liver and Gastrointestinal Research, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK.
University of Birmingham · GBCentre for Inflammation Research · GBUniversity Hospitals Birmingham NHS Foundation Trust · GBUniversity of Cambridge · GBUniversity of Turku · FIAston University · GBMinia University · EG

Funding

Cancer Research UK 26813Cancer Research UK 29959Medical Research Council MR/R010013/1Medical Research Council MR/T030798/2Medical Research Council MR/X00970X/1Wellcome Trust
6 · The paper itself

Abstract

Liver sinusoidal endothelial cells (LSEC) undergo significant phenotypic change in chronic liver disease (CLD), and yet the factors that drive this process and the impact on their function as a vascular barrier and gatekeeper for immune cell recruitment are poorly understood. Plasmalemma-vesicle-associated protein (PLVAP) has been characterized as a marker of LSEC in CLD; notably we found that PLVAP upregulation strongly correlated with markers of tissue senescence. Furthermore, exposure of human LSEC to the senescence-associated secretory phenotype (SASP) led to a significant upregulation of PLVAP. Flow-based assays demonstrated that SASP-driven leukocyte recruitment was characterized by paracellular transmigration of monocytes while the majority of lymphocytes migrated transcellularly. Knockdown studies confirmed that PLVAP selectively supported monocyte transmigration mediated through PLVAP's impact on LSEC permeability by regulating phospho-VE-cadherin expression and endothelial gap formation. PLVAP may therefore represent an endothelial target that selectively shapes the senescence-mediated immune microenvironment in liver disease.

Indexed as

Cell biologyMicroenvironmentMolecular biologyOmicsTranscriptomics

Identifiers

PMID37810232
PMCPMC10558774
OpenAlexW4386859161

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.