Evidence map›Paper›PMID 33189691›Full record

ArticleBrain research2021

Hedgehog signaling promotes endoneurial fibroblast migration and Vegf-A expression following facial nerve injury.

C Faniku, W Kong, L He, M Zhang, G Lilly, J P Pepper

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

Article in Brain research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Review
  5. Gli1 Regulates the Postnatal Acquisition of Peripheral Nerve Architecture.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022
    Article
  6. A State-of-the-Art of Functional Scaffolds for 3D Nervous Tissue Regeneration.Frontiers in bioengineering and biotechnology · 2021
    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

6 authors at 2 institutions in 1 country.

C FanikuDepartment of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
W KongInstitute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
L HeDepartment of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
M ZhangDepartment of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
G LillyDepartment of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, PV01, Portland, OR 97239, USA.
J P PepperDepartment of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA; Division of Facial Plastic & Reconstructive Surgery, Department of Otolaryngology - Head & Neck Surgery, Stanford University School of Medicine, 801 Welch Rd, Stanford, CA 94305, USA. Electronic address: jpepper@stanford.edu.
Stanford University · USOregon Health & Science University · US

Funding

Mechanisms of Regeneration: Facial Nerve Injury and RepairK08DE028364 · NIDCR · STANFORD UNIVERSITY · PI PEPPER, JON-PAUL · 2019 to 2023
$833k
NIDCR NIH HHS K08 DE028364
6 · The paper itself

Abstract

backgroundPeripheral nerve injuries are a common clinical problem which may result in permanent loss of motor or sensory function. A better understanding of the signaling pathways that lead to successful nerve regeneration may help in discovering new therapeutic targets. The Hedgehog (Hh) signaling pathway plays significant roles in nerve development and regeneration. In a mouse model of facial nerve injury, Hedgehog-responsive fibroblasts increase in number both at the site of injury and within the distal nerve. However, the role of these cells in facial nerve regeneration is not fully understood. We hypothesize that the Hh pathway plays an angiogenic and pro-migratory role following facial nerve injury.

methodsHedgehog pathway modulators were applied to murine endoneurial fibroblasts isolated from the murine facial nerve. The impact of pathway modulation on endoneurial fibroblast migration and cell proliferation was assessed. Gene expression changes of known Hedgehog target genes and the key angiogenic factor Vegf-A were determined by qPCR. In vivo, mice were treated with pathway agonist (SAG21k) and injured facial nerve specimens were analyzed via immunofluorescence and in situ hybridization.

resultsHedgehog pathway activation in facial nerve fibroblasts via SAG21k treatment increases Gli1 and Ptch1 expression, the rate of cellular migration, and Vegf-A expression in vitro. In vivo, expression of Gli1 and Vegf-A expression appears to increase after injury, particularly at the site of nerve injury and the distal nerve, as detected by immunofluorescence and in situ hybridization. Additionally, Gli1 transcripts co-localize with Vegf-A following transection injury to the facial nerve. DISCUSSION: These findings describe an angiogenic and pro-migratory role for the Hedgehog pathway mediated through effects on nerve fibroblasts. Given the critical role of Vegf-A in nerve regeneration, modulation of this pathway may represent a potential therapeutic target to improve facial nerve regeneration following injury.

Indexed as

AnimalsCell MovementCell ProliferationDisease Models, AnimalFacial NerveFacial Nerve InjuriesFemaleFibroblastsHedgehog ProteinsMaleMiceMice, Inbred C57BLNerve RegenerationPrimary Cell CultureSignal TransductionVascular Endothelial Growth Factor AHedgehog ProteinsVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseZinc Finger Protein GLI1AngiogenesisEndoneurial fibroblastFacial nerveHedgehog signalingNerve injuryNerve regenerationVascular endothelial growth factor A (Vegf-A)

Identifiers

PMID33189691
PMCPMC7772118
OpenAlexW3103054034

What OpenQuestion holds

Textmetadata
LicenceTDM
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.