Evidence map›Paper›PMID 25187433›Full record

ArticleThe Journal of pharmacology and experimental therapeutics2014

The procognitive and synaptogenic effects of angiotensin IV-derived peptides are dependent on activation of the hepatocyte growth factor/c-met system.

Caroline C Benoist, Leen H Kawas, Mingyan Zhu, Katherine A Tyson, Lori Stillmaker, Suzanne M Appleyard, John W Wright, Gary A Wayman, Joseph W Harding

RetractedOpen access · bronzeAbstract readRetracted Publication
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of pharmacology and experimental therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
1.7field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Therapeutic Peptides in Orthopaedics: Applications, Challenges, and Future Directions.Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2026
    Review
  4. Article
  5. Review
  6. The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. HGF and MET: From Brain Development to Neurological Disorders.Frontiers in cell and developmental biology · 2021
    Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Caroline C BenoistDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.).
Leen H KawasDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.).
Mingyan ZhuDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.).
Katherine A TysonDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.).
Lori StillmakerDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.).
Suzanne M AppleyardDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.).
John W WrightDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.).
Gary A WaymanDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.) hardingj@vetmed.wsu.edu waymang@vetmed.wsu.edu.
Joseph W HardingDepartment of Integrative Physiology and Neuroscience (C.C.B., L.H.K., M.Z., K.A.T., L.S., S.M.A., J.W.W., G.A.W., J.W.H.) and Department of Psychology (J.W.W., J.W.H.), Washington State University, Pullman, Washington; and M Biotechnology, Inc., Seattle, Washington (L.H.K., J.W.W., J.W.H.) hardingj@vetmed.wsu.edu waymang@vetmed.wsu.edu.
Washington State University · USAthira Pharma (United States) · US

Funding

Control of Dendritic and Synaptic Development by Extracellular CuesR01MH086032 · NIMH · WASHINGTON STATE UNIVERSITY · PI WAYMAN, GARY ALLEN · 2010 to 2014
$1.8M
NIMH NIH HHS R01 MH086032NIMH NIH HHS R01-MH086032
6 · The paper itself

Abstract

A subset of angiotensin IV (AngIV)-related molecules are known to possess procognitive/antidementia properties and have been considered as templates for potential therapeutics. However, this potential has not been realized because of two factors: 1) a lack of blood-brain barrier-penetrant analogs, and 2) the absence of a validated mechanism of action. The pharmacokinetic barrier has recently been overcome with the synthesis of the orally active, blood-brain barrier-permeable analog N-hexanoic-tyrosine-isoleucine-(6) aminohexanoic amide (dihexa). Therefore, the goal of this study was to elucidate the mechanism that underlies dihexa's procognitive activity. Here, we demonstrate that dihexa binds with high affinity to hepatocyte growth factor (HGF) and both dihexa and its parent compound Norleucine 1-AngIV (Nle(1)-AngIV) induce c-Met phosphorylation in the presence of subthreshold concentrations of HGF and augment HGF-dependent cell scattering. Further, dihexa and Nle(1)-AngIV induce hippocampal spinogenesis and synaptogenesis similar to HGF itself. These actions were inhibited by an HGF antagonist and a short hairpin RNA directed at c-Met. Most importantly, the procognitive/antidementia capacity of orally delivered dihexa was blocked by an HGF antagonist delivered intracerebroventricularly as measured using the Morris water maze task of spatial learning.

Indexed as

Angiotensin IIAnimalsCell LineCognitionDogsHEK293 CellsHippocampusHumansMadin Darby Canine Kidney CellsMaleOligopeptidesPeptidesPhosphorylationProto-Oncogene Proteins c-metRatsRats, Sprague-DawleyAngiotensin IIangiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-HGF activatorN-hexanoic-Tyr-Ile-(6) aminohexanoic amideOligopeptidesPeptidesProto-Oncogene Proteins c-metSerine Endopeptidases

Identifiers

PMID25187433
PMCPMC4201273
OpenAlexW1987192848

What OpenQuestion holds

Textmetadata
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.