Evidence map›Paper›PMID 24728340›Full record

ArticlePloS one2014

TGF-β-activated kinase 1 (TAK1) signaling regulates TGF-β-induced WNT-5A expression in airway smooth muscle cells via Sp1 and β-catenin.

Kuldeep Kumawat, Mark H Menzen, Ralph M Slegtenhorst, Andrew J Halayko, Martina Schmidt, Reinoud Gosens

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

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 38 citations in OpenAlex.

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  18. Distinct Roles of Wnt/Mediators of inflammation · 2017
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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

6 authors at 2 institutions in 2 countries.

Kuldeep KumawatDepartment of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, the Netherlands.
Mark H MenzenDepartment of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, the Netherlands.
Ralph M SlegtenhorstDepartment of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, the Netherlands.
Andrew J HalaykoDepartments of Physiology & Internal Medicine, University of Manitoba, Winnipeg, Canada.
Martina SchmidtDepartment of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, the Netherlands.
Reinoud GosensDepartment of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands; Groningen Research Institute for Asthma and COPD, University of Groningen, Groningen, the Netherlands.
University of Groningen · NLUniversity of Manitoba · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

WNT-5A, a key player in embryonic development and post-natal homeostasis, has been associated with a myriad of pathological conditions including malignant, fibroproliferative and inflammatory disorders. Previously, we have identified WNT-5A as a transcriptional target of TGF-β in airway smooth muscle cells and demonstrated its function as a mediator of airway remodeling. Here, we investigated the molecular mechanisms underlying TGF-β-induced WNT-5A expression. We show that TGF-β-activated kinase 1 (TAK1) is a critical mediator of WNT-5A expression as its pharmacological inhibition or siRNA-mediated silencing reduced TGF-β induction of WNT-5A. Furthermore, we show that TAK1 engages p38 and c-Jun N-terminal kinase (JNK) signaling which redundantly participates in WNT-5A induction as only simultaneous, but not individual, inhibition of p38 and JNK suppressed TGF-β-induced WNT-5A expression. Remarkably, we demonstrate a central role of β-catenin in TGF-β-induced WNT-5A expression. Regulated by TAK1, β-catenin is required for WNT-5A induction as its silencing repressed WNT-5A expression whereas a constitutively active mutant augmented basal WNT-5A abundance. Furthermore, we identify Sp1 as the transcription factor for WNT-5A and demonstrate its interaction with β-catenin. We discover that Sp1 is recruited to the WNT-5A promoter in a TGF-β-induced and TAK1-regulated manner. Collectively, our findings describe a TAK1-dependent, β-catenin- and Sp1-mediated signaling cascade activated downstream of TGF-β which regulates WNT-5A induction.

Indexed as

Gene Expression RegulationSignal Transductionbeta CateninCell Line, TransformedHumansJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 7MAP Kinase Kinase KinasesMyocytes, Smooth Musclep38 Mitogen-Activated Protein KinasesProtein BindingProto-Oncogene ProteinsSp1 Transcription FactorTransforming Growth Factor betaWnt-5a ProteinWnt Proteinsbeta CateninJNK Mitogen-Activated Protein KinasesMAP Kinase Kinase Kinase 7MAP Kinase Kinase Kinasesp38 Mitogen-Activated Protein KinasesProto-Oncogene ProteinsSp1 Transcription FactorTransforming Growth Factor betaWnt-5a ProteinWNT5A protein, humanWnt Proteins

Identifiers

PMID24728340
PMCPMC3984265
OpenAlexW1978498009

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.