Evidence map›Paper›PMID 26658708›Full record

ArticleBiology of reproduction2016

The MAPK/ERK-Signaling Pathway Regulates the Expression and Distribution of Tight Junction Proteins in the Mouse Proximal Epididymis.

Bongki Kim, Sylvie Breton

Open access · hybridAbstract read
In one paragraph

Article in Biology of reproduction, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
2.8field-weighted citation impact, top 10% 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

42 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. An Antioxidative Exopolysaccharide-Protein Complex ofAntioxidants (Basel, Switzerland) · 2025
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Claudin-4: A New Molecular Target for Epithelial Cancer Therapy.International journal of molecular sciences · 2023
    Review
  18. Article
  19. Article
  20. 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

2 authors at 2 institutions in 1 country.

Bongki KimCenter for Systems Biology, Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
Sylvie BretonCenter for Systems Biology, Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts breton.sylvie@mgh.harvard.edu.
Center for Systems Biology · USMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Transgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FLOREZ, JOSE CARLOS · 2000 to 2019
$31.4M
Transfer of grant 5R01HD040793 - Intercellular networks and luminal acidification in the male reproductive tractR01HD040793 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI BRETON, SYLVIE · 2001 to 2021
$6.6M
pH-sensing and activation of acid secretion by the V-ATPaseR01DK097124 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BRETON, SYLVIE · 2013 to 2016
$1.5M
NICHD NIH HHS R01 HD040793NICHD NIH HHS R01HD040793NIDDK NIH HHS DK43351NIDDK NIH HHS DK57521NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK057521NIDDK NIH HHS R01 DK097124NIDDK NIH HHS R01DK097124
6 · The paper itself

Abstract

The initial segment (IS) in rodents is functionally and structurally distinct from other epididymal segments and plays an important role in sperm maturation. The MAPK/ERK1/2 pathway is maintained active in the IS by testicular luminal factors and plays crucial roles in the maintenance and differentiation of the IS epithelium. Tight junctions (TJs) are constituents of the blood-epididymis barrier, which mediates the paracellular transport of ions, solutes, and water and controls epithelial cell differentiation, thereby contributing to the establishment of a unique luminal environment. We examine here the role of the MAPK/ERK1/2 pathway in the regulation of TJ proteins in the IS. Inhibition of mitogen activated protein kinase kinase (MAPKK or MEK1/2) with PD325901, followed by reduction of ERK1/2 phosphorylation (pERK), decreased zonula occludens (ZO)-2 expression and increased ZO-3 expression in TJs but had no effect on ZO-1 expression. In control mice, in addition to being located in TJs, claudin (Cldn)-1, Cldn-3, and Cldn-4 were detected in the basolateral membrane of epithelial cells, with enriched expression of Cldn-1 and Cldn-4 in basal cells. PD325901 reduced the expression of Cldn-1 and Cldn-4 at all locations without affecting Cldn-3. Occludin was undetectable in the IS of control mice, but PD325901 triggered its expression in TJs. No effect was observed for any of the proteins examined in the other epididymal regions. Our results indicate the participation of the MAPK/ERK1/2 pathway in the regulation of cell-cell events that control the formation and maintenance of the blood-epididymis barrier.

Indexed as

AnimalsApoptosisBenzamidesBlood-Testis BarrierCell MembraneClaudinsDiphenylamineEnzyme InhibitorsEpididymisEpithelial CellsMaleMAP Kinase Signaling SystemMiceMice, Inbred C57BLMitogen-Activated Protein KinasesPhosphorylationBenzamidesClaudinsDiphenylamineEnzyme InhibitorsmirdametinibMitogen-Activated Protein KinasesTight Junction ProteinsZonula Occludens-1 ProteinZonula Occludens-2 Proteinepididymisepithelial cell biologymale reproductive tract

Identifiers

PMID26658708
PMCPMC4809559
OpenAlexW2194338180

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.