Evidence map›Paper›PMID 27141442›Full record

ArticleTranslational andrology and urology2016

Brain-derived neurotrophic factor promotes nerve regeneration by activating the JAK/STAT pathway in Schwann cells.

Guiting Lin, Haiyang Zhang, Fionna Sun, Zhihua Lu, Amanda Reed-Maldonado, Yung-Chin Lee, Guifang Wang, Lia Banie, Tom F Lue

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

Article in Translational andrology and urology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing 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

36 citing papers in PubMed, 63 citations in OpenAlex.

  1. Article
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  3. Peripheral nerve repair: innovations and future directions.Journal of translational medicine · 2026
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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

9 authors at 5 institutions in 3 countries.

Guiting Lin1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Haiyang Zhang1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Fionna Sun1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Zhihua Lu1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Amanda Reed-Maldonado1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Yung-Chin Lee1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Guifang Wang1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Lia Banie1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Tom F Lue1 Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California, San Francisco, CA, USA ; 2 Minimally Invasive Urology Center, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250012, China ; 3 Department of Urology, The First Hospital of Jilin University, Changchun 130021, China ; 4 Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Jilin University · CNShandong Provincial Hospital · CNShandong University · CNUniversity of California, San Francisco · USKaohsiung Medical University Chung-Ho Memorial Hospital · TW

Funding

Prevention and Treatment of ImpotenceR37DK045370 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LUE, TOM F · 2004 to 2013
$3.5M
NIDDK NIH HHS R37 DK045370
6 · The paper itself

Abstract

backgroundRadical prostatectomy (RP) carries the risk of erectile dysfunction (ED) due to cavernous nerve (CN) injury. Schwann cells are essential for the maintenance of integrity and function of peripheral nerves such as the CNs. We hypothesize that brain-derived neurotrophic factor (BDNF) activates the Janus kinase (JAK)/(signal transducer and activator of transcription) STAT pathway in Schwann cells, not in neuronal axonal fibers, with the resultant secretion of cytokines from Schwann cells to facilitate nerve recovery.

methodsUsing four different cell lines-human neuroblastoma BE(2)-C and SH-SY5Y, human Schwann cell (HSC), and rat Schwann cell (RSC) RT4-D6P2T-we assessed the effect of BDNF application on the activation of the JAK/STAT pathway. We also assessed the time response of JAK/STAT pathway activation in RSCs and HSCs after BDNF treatment. We then assayed cytokine release from HSCs as a response to BDNF treatment using oncostatin M and IL6 as markers.

resultsWe showed extensive phosphorylation of STAT3/STAT1 by BDNF at high dose (100 pM) in RSCs, with no JAK/STAT pathway activation in human neuroblastoma cell lines. The time response of JAK/STAT pathway activation in RSCs and HSCs after BDNF treatment showed an initial peak at shortly after treatment and then a second higher peak at 24-48 hours. Cytokine release from HSCs increased progressively after BDNF application, reaching statistical significance for IL6.

conclusionsWe demonstrated for the first time the indirect mechanism of BDNF enhancement of nerve regeneration through the activation of JAK/STAT pathway in Schwann cells, rather than directly on neurons. As a result of BDNF application, Schwann cells produce cytokines that promote nerve regeneration.

Indexed as

Brain-derived neurotrophic factor (BDNF)cavernous nerve injury (CN injury)Janus kinase/signal transducer and activator of transcription (JAK/STAT)nerve regenerationSchwann cells

Identifiers

PMID27141442
PMCPMC4837308
OpenAlexW2294946878

What OpenQuestion holds

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Registered trials

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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.