Evidence map›Paper›PMID 27340942›Full record

ArticleStem cells (Dayton, Ohio)2016

Local CXCR4 Upregulation in the Injured Arterial Wall Contributes to Intimal Hyperplasia.

Xudong Shi, Lian-Wang Guo, Stephen Seedial, Toshio Takayama, Bowen Wang, Mengxue Zhang, Sarah R Franco, Yi Si, Mirnal A Chaudhary, Bo Liu and 1 more

Open access · hybridAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.9field-weighted citation impact, top 14% 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

15 citing papers in PubMed, 26 citations in OpenAlex.

  1. Article
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  3. Review
  4. Article
  5. Article
  6. Smad2 inhibition ofAtherosclerosis plus · 2021
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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

11 authors at 1 institution in 1 country.

Xudong ShiDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Lian-Wang GuoDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Stephen SeedialDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Toshio TakayamaDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Bowen WangDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Mengxue ZhangDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Sarah R FrancoDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Yi SiDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Mirnal A ChaudharyDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Bo LiuDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
K Craig KentDepartment of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
University of Wisconsin–Madison · US

Funding

TGF-Beta in Intimal Hyperplasia after Vascular BypassR01HL068673 · NHLBI · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI KENT, K CRAIG · 2002 to 2017
$4.9M
Vascular Surgery Research Training ProgramT32HL110853 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI MATSUMURA, JON STEVEN · 2012 to 2021
$2.6M
Graduate Training In Cellular And Molecular Pathogenesis Of Human DiseasesT32GM081061 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FABRY, ZSUZSANNA · 2010 to 2019
$1.8M
Sigma-1 Chaperone-Mediated in vivo Neuroprotection in the RetinaR01EY022678 · NEI · UNIVERSITY OF WISCONSIN-MADISON · PI GUO, LIANWANG · 2012 to 2016
$1.7M
Vascular smooth muscle cell apoptosis in intimal hyperplasiaR01HL122562 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI LIU, BO · 2015 to 2018
$1.6M
BET Bromodomain proteins as Novel Epigenetic Targets for prevention of Intimal Hyperplasia after Vascular SurgeryR01HL133665 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI GUO, LIANWANG · 2016 to 2019
$1.6M
NEI NIH HHS R01 EY022678NHLBI NIH HHS R01 HL068673NHLBI NIH HHS R01 HL122562NHLBI NIH HHS R01 HL133665NHLBI NIH HHS T32 HL110853NIGMS NIH HHS T32 GM081061
6 · The paper itself

Abstract

CXCR4 is a stem/progenitor cell surface receptor specific for the cytokine stromal cell-derived factor-1 (SDF-1α). There is evidence that bone marrow-derived CXCR4-expressing cells contribute to intimal hyperplasia (IH) by homing to the arterial subintima which is enriched with SDF-1α. We have previously found that transforming growth factor-β (TGFβ) and its signaling protein Smad3 are both upregulated following arterial injury and that TGFβ/Smad3 enhances the expression of CXCR4 in vascular smooth muscle cells (SMCs). It remains unknown, however, whether locally induced CXCR4 expression in SM22 expressing vascular SMCs plays a role in neointima formation. Here, we investigated whether elevated TGFβ/Smad3 signaling leads to the induction of CXCR4 expression locally in the injured arterial wall, thereby contributing to IH. We found prominent CXCR4 upregulation (mRNA, 60-fold; protein, 4-fold) in TGFβ-treated, Smad3-expressing SMCs. Chromatin immunoprecipitation assays revealed a specific association of the transcription factor Smad3 with the CXCR4 promoter. TGFβ/Smad3 treatment also markedly enhanced SDF-1α-induced ERK1/2 phosphorylation as well as SMC migration in a CXCR4-dependent manner. Adenoviral expression of Smad3 in balloon-injured rat carotid arteries increased local CXCR4 levels and enhanced IH, whereas SMC-specific depletion of CXCR4 in the wire-injured mouse femoral arterial wall produced a 60% reduction in IH. Our results provide the first evidence that upregulation of TGFβ/Smad3 in injured arteries induces local SMC CXCR4 expression and cell migration, and consequently IH. The Smad3/CXCR4 pathway may provide a potential target for therapeutic interventions to prevent restenosis. Stem Cells 2016;34:2744-2757.

Indexed as

AnimalsCarotid ArteriesCarotid Artery InjuriesCell MovementGene Expression RegulationMaleMiceMice, KnockoutMicrofilament ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Muscle ProteinsMyocytes, Smooth MuscleNeointimaPhosphorylationPrimary Cell CultureCXCR4 protein, mouseMapk1 protein, mouseMicrofilament ProteinsMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Muscle ProteinsReceptors, CXCR4Smad3 ProteinSmad3 protein, mouseTagln protein, mouseTransforming Growth Factor betaCXCR4/SDF-1αintimal hyperplasiasmooth muscle cell migrationsmooth muscle cell specific CXCR4 knockoutTGFβ/Smad3

Identifiers

PMID27340942
PMCPMC5113668
OpenAlexW2473324139

What OpenQuestion holds

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LicenceCC BY-NC
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.