Evidence map›Paper›PMID 24962629›Full record

ArticleJournal of cellular physiology2015

TGF-β1 Suppresses Plasmin and MMP Activity in Flexor Tendon Cells via PAI-1: Implications for Scarless Flexor Tendon Repair.

Youssef M Farhat, Alaa A Al-Maliki, Anas Easa, Regis J O'Keefe, Edward M Schwarz, Hani A Awad

Open access · greenAbstract read
In one paragraph

Article in Journal of cellular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
1.3field-weighted citation impact, top 23% 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

23 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. PAI-1 mediates TGF-β1-induced myofibroblast activation in tenocytes via mTOR signaling.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023
    Article
  11. Article
  12. Review
  13. Article
  14. Transcriptomic Analysis of Cellular Pathways in Healing Flexor Tendons of Plasminogen Activator Inhibitor 1 (PAI-1/Serpine1) Null Mice.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2020
    Article
  15. Article
  16. Tendon stem progenitor cells: Understanding the biology to inform therapeutic strategies for tendon repair.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2019
    Review
  17. Review
  18. Article
  19. [Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2017
    Article
  20. Cell and Biologic-Based Treatment of Flexor Tendon Injuries.Operative techniques in orthopaedics · 2016
    Article
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 1 institution in 1 country.

Youssef M FarhatDepartment of Biomedical Engineering, 601 Elmwood Ave, Rochester, New York.
Alaa A Al-MalikiThe Center for Musculoskeletal Research, 601 Elmwood Ave, Rochester, New York.
Anas EasaThe Center for Musculoskeletal Research, 601 Elmwood Ave, Rochester, New York.
Regis J O'KeefeThe Center for Musculoskeletal Research, 601 Elmwood Ave, Rochester, New York.
Edward M SchwarzThe Center for Musculoskeletal Research, 601 Elmwood Ave, Rochester, New York.
Hani A AwadDepartment of Biomedical Engineering, 601 Elmwood Ave, Rochester, New York.
University of Rochester · US

Funding

University of Rochester Mentoring Environment: Nurturing Training Opportunities in Research (UR-MENTOR)T32GM007356 · NIGMS · UNIVERSITY OF ROCHESTER · PI O'BANION, M. KERRY · 1985 to 2023
$15.1M
Engineering scarless repair of flexor tendon injuriesR01AR056696 · NIAMS · UNIVERSITY OF ROCHESTER · PI AWAD, HANI A, BENOIT, DANIELLE S. · 2009 to 2019
$3.6M
Training in Orthopaedic Researchhttps://apps.era.nih.gov/grantfolder/viewInternalGF.era?applId=8841318&folderId=90T32AR053459 · NIAMS · UNIVERSITY OF ROCHESTER · PI ZUSCIK, MICHAEL J · 2006 to 2017
$3.4M
The University of Rochester Core Center for Musculoskeletal Biology and MedicineP30AR061307 · NIAMS · UNIVERSITY OF ROCHESTER · PI SCHWARZ, EDWARD M. · 2011 to 2015
$3.0M
NIAMS NIH HHS P30 AR061307NIAMS NIH HHS P30AR061307NIAMS NIH HHS R01 AR056696NIAMS NIH HHS R01AR056696NIAMS NIH HHS T32 AR053459NIGMS NIH HHS T32 GM007356NIGMS NIH HHS T32 GM07356
6 · The paper itself

Abstract

Flexor tendon injuries caused by deep lacerations to the hands are a challenging problem as they often result in debilitating adhesions that prevent the movement of the afflicted fingers. Evidence exists that tendon adhesions as well as scarring throughout the body are largely precipitated by the pleiotropic growth factor, Transforming Growth Factor Beta 1(TGF-β1), but the effects of TGF-β1 are poorly understood in tendon healing. Using an in vitro model of tendon healing, we previously found that TGF-β1 causes gene expression changes in tenocytes that are consistent with scar tissue and adhesion formation, including upregulation of the anti-fibrinolytic protein, PAI-1. Therefore, we hypothesized that TGF-β1 contributes to scarring and adhesions by reducing the activity of proteases responsible for ECM degradation and remodeling, such as plasmin and MMPs, via upregulation of PAI-1. To test our hypothesis, we examined the effects of TGF-β1 on the protease activity of tendon cells. We found that flexor tendon tenocytes treated with TGF-β1 had significantly reduced levels of active MMP-2 and plasmin. Interestingly, the effects of TGF-β1 on protease activity were completely abolished in tendon cells from homozygous plasminogen activator inhibitor 1 (PAI-1) knockout (KO) mice, which are unable to express PAI-1. Our findings support the hypothesis that TGF-β1 induces PAI-1, which suppresses plasmin and plasmin-mediated MMP activity, and provide evidence that PAI-1 may be a novel therapeutic target for preventing adhesions and promoting a scarless, regenerative repair of flexor tendon injuries.

Indexed as

AnimalsCells, CulturedFibrinolysinFibronectinsMatrix MetalloproteinasesMice, Inbred C57BLMice, KnockoutPlasminogen Activator Inhibitor 1Serpin E2TendonsTransforming Growth Factor beta1Wound HealingFibrinolysinFibronectinsMatrix MetalloproteinasesPlasminogen Activator Inhibitor 1Serpin E2Serpine2 protein, mouseTransforming Growth Factor beta1

Identifiers

PMID24962629
PMCPMC4276543
OpenAlexW1580752873

What OpenQuestion holds

Textmetadata
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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.