Evidence map›Paper›PMID 25658447›Full record

ArticlePloS one2015

PACAP interacts with PAC1 receptors to induce tissue plasminogen activator (tPA) expression and activity in schwann cell-like cultures.

Alessandro Castorina, James A Waschek, Rubina Marzagalli, Venera Cardile, Filippo Drago

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.7field-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

20 citing papers in PubMed, 32 citations in OpenAlex.

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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

5 authors at 2 institutions in 2 countries.

Alessandro CastorinaDepartment of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, University of Catania, Catania, Italy.
James A WaschekSemel Institute/Department of Psychiatry, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Rubina MarzagalliDepartment of Biomedical Sciences and Biotechnologies, Section of Human Anatomy and Histology, University of Catania, Catania, Italy.
Venera CardileDepartment of Biomedical Sciences and Biotechnologies, Section of Physiology, University of Catania, Catania, Italy.
Filippo DragoDepartment of Biomedical Sciences and Biotechnologies, Section of Pharmacology, University of Catania, Catania, Italy.
University of Catania · ITUniversity of California, Los Angeles · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Regeneration of peripheral nerves depends on the abilities of rejuvenating axons to migrate at the injury site through cellular debris and altered extracellular matrix, and then grow along the residual distal nerve sheath conduit and reinnervate synaptic targets. Considerable evidence suggest that glial cells participate in this process, although the mechanisms remain to be clarified. In cell culture, regenerating neurites secrete PACAP, a peptide shown to induce the expression of the protease tissue plasminogen activator (tPA) in neural cell types. In the present studies, we tested the hypothesis that PACAP can stimulate peripheral glial cells to produce tPA. More specifically, we addressed whether or not PACAP promoted the expression and activity of tPA in the Schwann cell line RT4-D6P2T, which shares biochemical and physical properties with Schwann cells. We found that PACAP dose- and time-dependently stimulated tPA expression both at the mRNA and protein level. Such effect was mimicked by maxadilan, a potent PAC1 receptor agonist, but not by the PACAP-related homolog VIP, suggesting a PAC1-mediated function. These actions appeared to be mediated at least in part by the Akt/CREB signaling cascade because wortmannin, a PI3K inhibitor, prevented peptide-driven CREB phosphorylation and tPA increase. Interestingly, treatment with BDNF mimicked PACAP actions on tPA, but acted through both the Akt and MAPK signaling pathways, while causing a robust increase in PACAP and PAC1 expression. PACAP6-38 totally blocked PACAP-driven tPA expression and in part hampered BDNF-mediated effects. We conclude that PACAP, acting through PAC1 receptors, stimulates tPA expression and activity in a Akt/CREB-dependent manner to promote proteolytic activity in Schwann-cell like cultures.

Indexed as

AnimalsBrain-Derived Neurotrophic FactorCell LineDose-Response Relationship, DrugGene ExpressionPituitary Adenylate Cyclase-Activating PolypeptideProto-Oncogene Proteins c-aktRatsReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type ISchwann CellsSignal TransductionTissue Plasminogen ActivatorBrain-Derived Neurotrophic FactorPituitary Adenylate Cyclase-Activating PolypeptideProto-Oncogene Proteins c-aktReceptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type ITissue Plasminogen Activator

Identifiers

PMID25658447
PMCPMC4319891
OpenAlexW2080357358

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.