Evidence map›Paper›PMID 35861713›Full record

ArticleeLife2022

Claudin5 protects the peripheral endothelial barrier in an organ and vessel-type-specific manner.

Mark Richards, Emmanuel Nwadozi, Sagnik Pal, Pernilla Martinsson, Mika Kaakinen, Marleen Gloger, Elin Sjöberg, Katarzyna Koltowska, Christer Betsholtz, Lauri Eklund and 2 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. 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
3.9field-weighted citation impact, top 5% 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, 48 citations in OpenAlex.

  1. Arteriosclerosis, thrombosis, and vascular biology · 2026
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  16. The vascular endothelium as decision maker in lung injury.Frontiers in cell and developmental biology · 2025
    Review
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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

12 authors at 2 institutions in 3 countries.

Mark RichardsDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-2266-3329
Emmanuel NwadoziDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Sagnik PalDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-5562-1555
Pernilla MartinssonDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Mika KaakinenOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.
Marleen GlogerDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-3319-7642
Elin SjöbergDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-8799-4874
Katarzyna KoltowskaDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID 0000-0002-6841-8900
Christer BetsholtzDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Lauri EklundOulu Center for Cell-Matrix Research, Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu, Oulu, Finland.ORCID 0000-0002-3177-7504
Sofia Nordling *Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Lena Claesson-Welsh *Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.ORCID 0000-0003-4275-2000
Uppsala University · SEMatrix Research (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysfunctional and leaky blood vessels resulting from disruption of the endothelial cell (EC) barrier accompanies numerous diseases. The EC barrier is established through endothelial cell tight and adherens junctions. However, the expression pattern and precise contribution of different junctional proteins to the EC barrier is poorly understood. Here, we focus on organs with continuous endothelium to identify structural and functional in vivo characteristics of the EC barrier. Assembly of multiple single-cell RNAseq datasets into a single integrated database revealed the variability and commonalities of EC barrier patterning. Across tissues, Claudin5 exhibited diminishing expression along the arteriovenous axis, correlating with EC barrier integrity. Functional analysis identified tissue-specific differences in leakage properties and response to the leakage agonist histamine. Loss of Claudin5 enhanced histamine-induced leakage in an organotypic and vessel type-specific manner in an inducible, EC-specific, knock-out mouse. Mechanistically, Claudin5 loss left junction ultrastructure unaffected but altered its composition, with concomitant loss of zonula occludens-1 and upregulation of VE-Cadherin expression. These findings uncover the organ-specific organisation of the EC barrier and distinct importance of Claudin5 in different vascular beds, providing insights to modify EC barrier stability in a targeted, organ-specific manner.

Indexed as

Adherens JunctionsHistamineAnimalsCadherinsClaudin-5Endothelial CellsEndotheliumMiceTight JunctionsCadherinsClaudin-5Cldn5 protein, mouseHistaminecell biologyClaudin 5endothelial cellmouseorganotypicityvascular permeability

Identifiers

PMID35861713
PMCPMC9348850
OpenAlexW4286111084

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.