Evidence map›Paper›PMID 34345888›Full record

ArticleJournal of cell science2021

Phosphorylated cingulin localises GEF-H1 at tight junctions to protect vascular barriers in blood endothelial cells.

Silvio Holzner, Sophie Bromberger, Judith Wenzina, Karin Neumüller, Tina-Maria Holper, Peter Petzelbauer, Wolfgang Bauer, Benedikt Weber, Klaudia Schossleitner

Open access · hybridAbstract read
In one paragraph

Article in Journal of cell science, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 13 citations in OpenAlex.

  1. Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026
    Review
  2. Characterization of Corneal Defects in ATG7-Deficient Mice.International journal of molecular sciences · 2025
    Article
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. 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

9 authors at 1 institution in 1 country.

Silvio HolznerDepartment of Dermatology, Skin and Endothelium Research Division, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0003-4331-3878
Sophie BrombergerDepartment of Dermatology, Skin and Endothelium Research Division, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0002-8177-3878
Judith WenzinaDepartment of Dermatology, Skin and Endothelium Research Division, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0002-3423-7423
Karin NeumüllerDepartment of Dermatology, Skin and Endothelium Research Division, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0001-5430-7049
Tina-Maria HolperDepartment of Dermatology, Medical University of Vienna, 1090, Vienna, Austria.
Peter PetzelbauerDepartment of Dermatology, Skin and Endothelium Research Division, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0001-7080-5259
Wolfgang BauerDepartment of Dermatology, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0002-0155-1176
Benedikt WeberDepartment of Dermatology, Skin and Endothelium Research Division, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0002-7217-4590
Klaudia SchossleitnerDepartment of Dermatology, Skin and Endothelium Research Division, Medical University of Vienna, 1090, Vienna, Austria.ORCID 0000-0003-1202-5961
Medical University of Vienna · AT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dysfunction of vascular barriers is a critical step in inflammatory diseases. Endothelial tight junctions (TJs) control barrier function, and the cytoplasmic adaptor protein cingulin connects TJs to signalling pathways. However, local events at TJs during inflammation are largely unknown. In this study, we investigate the local response of TJ adaptor protein cingulin and its interaction with Rho guanine nucleotide exchange factor H1 (GEF-H1, also known as ARHGEF2) upon vascular barrier disruption to find a new approach to counteract vascular leak. Based on transendothelial-electrical-resistance (TEER) measurements, cingulin strengthened barrier integrity upon stimulation with histamine, thrombin and VEGF. Cingulin also attenuated myosin light chain 2 (MLC2; also known as MYL2) phosphorylation by localising GEF-H1 to cell junctions. By using cingulin phosphomutants, we verified that the phosphorylation of the cingulin head domain is required for its protective effect. Increased colocalisation of GEF-H1 and cingulin was observed in the vessels of vasculitis patients compared to those in healthy skin. Our findings demonstrate that cingulin can counteract vascular leak at TJs, suggesting the existence of a novel mechanism in blood endothelial cells that protects barrier function during disease.

Indexed as

Endothelial CellsTight JunctionsCapillary PermeabilityGuanine Nucleotide Exchange FactorsHumansRho Guanine Nucleotide Exchange FactorsSignal TransductionGuanine Nucleotide Exchange FactorsRho Guanine Nucleotide Exchange FactorsAMPKCingulinEndotheliumGuanine nucleotide exchange factorsTight junctionVascular barrier function

Identifiers

PMID34345888
PMCPMC8445606
OpenAlexW3192745632

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.