Evidence map›Paper›PMID 34299018›Full record

ArticleInternational journal of molecular sciences2021

Expression of Connexin43 Stimulates Endothelial Angiogenesis Independently of Gap Junctional Communication In Vitro.

Christoph Koepple, Zizi Zhou, Lena Huber, Matthias Schulte, Kjestine Schmidt, Torsten Gloe, Ulrich Kneser, Volker Jürgen Schmidt, Cor de Wit

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

  1. Beyond the gap: moonlighting functions of connexins in cancer.Cell communication and signaling : CCS · 2026
    Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
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 4 institutions in 2 countries.

Christoph KoeppleDepartment for Hand Surgery, Plastic Surgery and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Heidelberg University, 67071 Ludwigshafen, Germany.
Zizi ZhouDepartment for Hand Surgery, Plastic Surgery and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Heidelberg University, 67071 Ludwigshafen, Germany.ORCID 0000-0002-9715-3665
Lena HuberDepartment for Hand Surgery, Plastic Surgery and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Heidelberg University, 67071 Ludwigshafen, Germany.
Matthias SchulteDepartment for Hand Surgery, Plastic Surgery and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Heidelberg University, 67071 Ludwigshafen, Germany.
Kjestine SchmidtInstitut für Physiologie, Universität zu Lübeck, 23562 Lübeck, Germany.
Torsten GloePhysiology, Institute of Theoretical Medicine, Universität Augsburg, 86159 Augsburg, Germany.
Ulrich KneserDepartment for Hand Surgery, Plastic Surgery and Reconstructive Surgery, BG Trauma Center Ludwigshafen, Heidelberg University, 67071 Ludwigshafen, Germany.ORCID 0000-0002-3402-2860
Volker Jürgen SchmidtDepartment for Plastic Surgery and Breast Surgery, Zealand University Hospital (SUH) Roskilde, Copenhagen University, 4000 Roskilde, Denmark.
Cor de WitInstitut für Physiologie, Universität zu Lübeck, 23562 Lübeck, Germany.ORCID 0000-0003-4621-0399
Heidelberg University · DEGerman Centre for Cardiovascular Research · DEUniversity of Augsburg · DEZealand University Hospital · DK

Funding

Deutsches Zentrum für Herz-Kreislaufforschung FKZ: 81Z0700106
6 · The paper itself

Abstract

Connexins (Cx) form gap junctions (GJ) and allow for intercellular communication. However, these proteins also modulate gene expression, growth, and cell migration. The downregulation of Cx43 impairs endothelial cell migration and angiogenetic potential. Conversely, endothelial Cx43 expression is upregulated in an in vivo angiogenesis model relying on hemodynamic forces. We studied the effects of Cx43 expression on tube formation and proliferation in HUVECs and examined its dependency on GJ communication. Expectedly, intercellular communication assessed by dye transfer was linked to Cx43 expression levels in HUVECs and was sensitive to a GJ blockade by the Cx43 mimetic peptide Gap27. The proliferation of HUVECs was not affected by Cx43 overexpression using Cx43 cDNA transfection, siRNA-mediated knockdown of Cx43, or the inhibition of GJ compared to the controls (transfection of an empty vector, scrambled siRNA, and the solvent). In contrast, endothelial tube and sprout formation in HUVECs was minimized after Cx43 knockdown and significantly enhanced after Cx43 overexpression. This was not affected by a GJ blockade (Gap27). We conclude that Cx43 expression positively modulates the angiogenic potential of endothelial cells independent of GJ communication. Since proliferation remained unaffected, we suggest that Cx43 protein may modulate endothelial cell migration, thereby supporting angiogenesis. The modulation of Cx43 expression may represent an exploitable principle for angiogenesis induction in clinical therapy.

Indexed as

Cell CommunicationCell MovementCell ProliferationConnexin 43ConnexinsEndothelial CellsGap JunctionsGene ExpressionGene Knockdown TechniquesHumansHuman Umbilical Vein Endothelial CellsIn Vitro TechniquesNeovascularization, PhysiologicOligopeptidesReal-Time Polymerase Chain ReactionRNA, Small InterferingConnexin 43Connexinsgap 27 peptideOligopeptidesRNA, Small Interferingcellular migrationconnexinsendothelial tube formationgap junctionshuman umbilical vein endothelial cells

Identifiers

PMID34299018
PMCPMC8306600
OpenAlexW3182959035

What Socratic 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 Socratic graph.