Evidence map›Paper›PMID 29170419›Full record

ArticleScientific reports2017

PDGFR Signaling Mediates Hyperproliferation and Fibrotic Responses of Subsynovial Connective Tissue Cells in Idiopathic Carpal Tunnel Syndrome.

Yuki Saito, Takako Chikenji, Yasuhiro Ozasa, Mineko Fujimiya, Toshihiko Yamashita, Anne Gingery, Kousuke Iba

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
0.9field-weighted citation impact, top 26% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 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

7 authors at 2 institutions in 2 countries.

Yuki SaitoDepartment of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan.ORCID 0000-0002-7949-1628
Takako ChikenjiDepartment of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan. chikenji@sapmed.ac.jp.ORCID 0000-0003-2832-3656
Yasuhiro OzasaDepartment of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Mineko FujimiyaDepartment of Anatomy, Sapporo Medical University School of Medicine, Sapporo, Japan.
Toshihiko YamashitaDepartment of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Anne GingeryDepartment of Orthopedic Surgery, Mayo Clinic, Rochester, United States.
Kousuke IbaDepartment of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan.
Sapporo Medical University · JPMayo Clinic · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Fibrosis of the subsynovial connective tissue (SSCT) is a pathognomonic change in carpal tunnel syndrome (CTS). Identification of molecular targets and anti-fibrotic therapies could provide new treatment strategies for CTS. The contribution of SSCT cells to fibrosis and the signaling pathways that initiate and aggravate fibrosis in CTS remain unknown. Here we report that platelet-derived growth factor receptor alpha (PDGFRα) positive ( + ) cells accumulate in CTS SSCT and that the presence of fibrotic growth factor, PDGF-AA, results in increased proliferation of PDGFRα+ cells via PI3K/Akt signaling pathway. Although PI3K inhibition decreased proliferation, there was no change in fibrosis-related gene expression. Indeed, protein levels of fibrosis signaling mediator TGF-β remained the same and the second messenger, Smad2/3, accumulated in the nucleus. In contrast AMP-activated protein kinase (AMPK) activation, which can be induced with metformin and AICAR inhibited proliferation, TGF-β expression, and altered cell morphology in SSCT cells. Further we show that AMPK activation by metformin reduced collagen III levels and the ratio of Collagen I to Collagen III. Both AICAR and metformin reduced F-actin and significantly reduced the fiber cross alignment. Our results suggest that PDGFRa signaling may be an important fibrosis target and that activators of AMPK, may be an important therapeutic approach for treating CTS.

Indexed as

Carpal Tunnel SyndromeCell ProliferationConnective TissueEnzyme-Linked Immunosorbent AssayFemaleFlow CytometryHumansImmunohistochemistryMaleMiddle AgedOncogene Protein v-aktPhosphatidylinositol 3-KinasesPlatelet-Derived Growth FactorReal-Time Polymerase Chain ReactionReceptor, Platelet-Derived Growth Factor alphaSignal TransductionOncogene Protein v-aktPhosphatidylinositol 3-KinasesPlatelet-Derived Growth Factorplatelet-derived growth factor AReceptor, Platelet-Derived Growth Factor alpha

Identifiers

PMID29170419
PMCPMC5700922
OpenAlexW2770531172

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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.