Evidence map›Paper›PMID 34489407›Full record

ArticleNature communications2021

Disrupting biological sensors of force promotes tissue regeneration in large organisms.

Kellen Chen, Sun Hyung Kwon, Dominic Henn, Britta A Kuehlmann, Ruth Tevlin, Clark A Bonham, Michelle Griffin, Artem A Trotsyuk, Mimi R Borrelli, Chikage Noishiki and 18 more

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

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% 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

68 citing papers in PubMed, 1 synthesis or guideline pooled it, 89 citations in OpenAlex.

  1. Fibroblasts in Scar Formation: Biology and Clinical Translation.Oxidative medicine and cellular longevity · 2022
    Pooled it
  2. Article
  3. A practical toolbox for modelling fibrosis in vitro.Nature biomedical engineering · 2026
    Review
  4. Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Characterization of cutaneous wound healing in swine.JID innovations : skin science from molecules to population health · 2026
    Article
  12. Review
  13. Review
  14. Article
  15. Burn Selection: How Fire Injury Shaped Human Evolution.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026
    Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article

8 more citing papers are in PubMed but not listed here.

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

28 authors at 3 institutions in 2 countries.

Kellen Chen *Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-7023-7850
Sun Hyung Kwon *Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Dominic Henn *Department of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Britta A KuehlmannDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Ruth TevlinDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Clark A BonhamDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Michelle GriffinDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Artem A TrotsyukDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Mimi R BorrelliDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Chikage NoishikiDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Jagannath PadmanabhanDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-1096-6637
Janos A BarreraDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0001-6811-8337
Zeshaan N MaanDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Teruyuki DohiDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Chyna J MaysDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-0393-0735
Autumn H GrecoDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0002-7557-6800
Dharshan SivarajDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
John Q LinDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Tobias FehlmannClinical Bioinformatics, Saarland University, Saarbruecken, Germany.ORCID 0000-0003-1967-2918
Alana M Mermin-BunnellDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-1100-6072
Smiti MittalDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Michael S HuDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Alsu I ZamaleevaBiomaterials and Advanced Drug Delivery Laboratory, Stanford University, Stanford, CA, USA.
Andreas KellerClinical Bioinformatics, Saarland University, Saarbruecken, Germany.ORCID 0000-0002-5361-0895
Jayakumar RajadasBiomaterials and Advanced Drug Delivery Laboratory, Stanford University, Stanford, CA, USA.
Michael T LongakerDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID 0000-0003-1430-8914
Michael JanuszykDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Geoffrey C GurtnerDepartment of Surgery, Division of Plastic and Reconstructive Surgery, Stanford University School of Medicine, Stanford, CA, USA. ggurtner@stanford.edu.
Stanford University · USSaarland University · DEUniversity Hospital Regensburg · DE

Funding

Center for Dental, Oral, and Craniofacial Tissue and Organ Regeneration (C-DOCTOR)U24DE029463 · NIDCR · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CHAI, YANG, LOTZ, JEFFREY C. · 2020 to 2024
$29.5M
Stanford Islet Research CoreP30DK116074 · NIDDK · STANFORD UNIVERSITY · PI Holden T. Maecker · 2017 to 2026
$19.5M
Center for Dental, Oral, and Craniofacial Tissue and Organ Regeneration (C-DOCTOR)U24DE026914 · NIDCR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAI, YANG, CHEN, YONG · 2017 to 2019
$12.0M
Building Interdisciplinary Research Careers in Womens Health at UC Davis - Administrative SupplementK12HD051958 · NICHD · UNIVERSITY OF CALIFORNIA DAVIS · PI LANE, NANCY E · 2005 to 2023
$9.6M
Ultra high throughput sequencer for sustaining and enhancing multi-scale genomic studiesS10OD025212 · OD · STANFORD UNIVERSITY · PI SNYDER, MICHAEL P. · 2018 to 2018
$600k
High Throughput DNA Sequencer UpgradeS10OD018220 · OD · STANFORD UNIVERSITY · PI COLLER, JOHN · 2014 to 2014
$596k
Computer ClusterS10OD021763 · OD · STANFORD UNIVERSITY · PI JI, HANLEE P · 2016 to 2016
$481k
NICHD NIH HHS K12 HD051958NIDCR NIH HHS U24 DE026914NIDCR NIH HHS U24 DE029463NIDDK NIH HHS P30 DK116074NIH HHS S10 OD018220NIH HHS S10 OD021763NIH HHS S10 OD025212
6 · The paper itself

Abstract

Tissue repair and healing remain among the most complicated processes that occur during postnatal life. Humans and other large organisms heal by forming fibrotic scar tissue with diminished function, while smaller organisms respond with scarless tissue regeneration and functional restoration. Well-established scaling principles reveal that organism size exponentially correlates with peak tissue forces during movement, and evolutionary responses have compensated by strengthening organ-level mechanical properties. How these adaptations may affect tissue injury has not been previously examined in large animals and humans. Here, we show that blocking mechanotransduction signaling through the focal adhesion kinase pathway in large animals significantly accelerates wound healing and enhances regeneration of skin with secondary structures such as hair follicles. In human cells, we demonstrate that mechanical forces shift fibroblasts toward pro-fibrotic phenotypes driven by ERK-YAP activation, leading to myofibroblast differentiation and excessive collagen production. Disruption of mechanical signaling specifically abrogates these responses and instead promotes regenerative fibroblast clusters characterized by AKT-EGR1.

Indexed as

AnimalsCell DifferentiationCells, CulturedCollagenFemaleFibroblastsFocal Adhesion Kinase 1Guided Tissue RegenerationHumansIndolesMechanotransduction, CellularSequence Analysis, RNASingle-Cell AnalysisSkinSkin Physiological PhenomenaStress, MechanicalCollagenFocal Adhesion Kinase 1IndolesN-methyl-N-(3-((2-(2-oxo-2,3-dihydro-1H-indol-5-ylamino)-5-trifluoromethyl-pyrimidin-4-ylamino)-methyl)-pyridin-2-yl)-methanesulfonamidePTK2 protein, humanSulfonamides

Identifiers

PMID34489407
PMCPMC8421385
OpenAlexW3196297610

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.