CoChat
Sign Up
Cited by 149Muscle Physiology and DisordersExercise and Physiological ResponsesCytokine Signaling Pathways and Interactions

Association of Interleukin-6 Signalling with the Muscle Stem Cell Response Following Muscle-Lengthening Contractions in Humans

Open access
McKay, Bryon R., De Lisio, Michael, Johnston, Adam P. W., O'Reilly, Ciara E., Phillips, Stuart M., Tarnopolsky, Mark A., Parise, Gianni·2009·PLoS ONE
DOI 10.1371/journal.pone.0006027PMC PMC2696599
Open this paper in CoChat — free accountOpen PDF

Abstract

BACKGROUND: The regulation of muscle stem cells in humans in response to muscle injury remains largely undefined. Recently, interleukin-6 (IL-6) has been implicated in muscle stem cell (satellite cell)-mediated muscle hypertrophy in animals; however, the role of IL-6 in the satellite cell (SC) response following muscle-lengthening contractions in humans has not been studied. METHODOLOGY/PRINCIPAL FINDINGS: Eight subjects (age 22+/-1 y; 79+/-8 kg) performed 300 maximal unilateral lengthening contractions (3.14 rad.s(-1)) of the knee extensors. Blood and muscle samples were collected before and at 4, 24, 72, and 120 hours post intervention. IL-6, IL-6 receptor, IL-6R(alpha), cyclin D1, suppressor of cytokine signling-3 (SOCS3) mRNA were measured using quantitative RT-PCR and serum IL-6 protein was measured using an ELISA kit. JAK2 and STAT3 phosphorylated and total protein was measured using western blotting techniques. Immunohistochemical analysis of muscle cross-sections was performed for the quantification of SCs (Pax7(+) cells) as well as the expression of phosphorylated STAT3, IL-6, IL-6R(alpha), and PCNA across all time-points. The SC response, as defined by an amplification of Pax7(+) cells, was rapid, increasing by 24 h and peaking 72 h following the intervention. Muscle IL-6 mRNA increased following the intervention, which correlated strongly (R(2) = 0.89, p<0.002) with an increase in serum IL-6 concentration. SC IL-6R(alpha) protein was expressed on the fiber, but was also localized to the SC, and IL-6(+) SC increased rapidly following muscle-lengthening contractions and returned to basal levels by 72 h post-intervention, demonstrating an acute temporal expression of IL-6 with SC. Phosphorylated STAT3 was evident in SCs 4 h after lengthening contraction, and the downstream genes, cyclin D1 and SOCS3 were significantly elevated 24 hours after the intervention. CONCLUSIONS/SIGNIFICANCE: The increased expression of STAT3 responsive genes and expression of IL-6 within SCs demonstrate that IL-6/STAT3 signaling occurred in SCs, correlating with an increase in SC proliferation, evidenced by increased Pax7(+)/PCNA(+) cell number in the early stages of the time-course. Collectively, these data illustrate that IL-6 is an important signaling molecule associated with the SC response to acute muscle-lengthening contractions in humans.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0006027

Cites

64 of 64 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Acute transient increases in inflammation play an important part in early regenerative processes of muscle adaptation, particularly in response to exercise.

    “Acute transient increases in inflammation plays an important part in the early regenerative processes of muscle adaptation, particularly in response to exercise [54,55].”

    From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [54]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
McKay, B. R., De Lisio, M., Johnston, A. P. W., O'Reilly, C. E., Phillips, S. M., Tarnopolsky, M. A., & Parise, G.
Affiliations
McMaster University (CA)
Corresponding author
Parise, Gianni
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-06-24
Volume
4
Issue
6
Pages
e6027
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0006027
PMC
PMC2696599
OpenAlex
W2081080799
Cited by
149
References
64
Citations by year
2026: 6 · 2025: 3 · 2024: 7 · 2023: 8 · 2022: 4 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 7 · 2017: 13 · 2016: 14 · 2015: 8 · 2014: 14 · 2013: 16 · 2012: 11
FWCI
3.35
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • IslandScholar (University of Prince Edward Island) (submittedVersion, cc-by)
Funders
Natural Sciences and Engineering Research Council of Canada
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interleukin-6, satellite cells, muscle stem cells, eccentric contraction, muscle damage, STAT3 signaling, IL-6 receptor alpha, SOCS3, cyclin D1, JAK2, Pax7, muscle regeneration, knee extensors, muscle hypertrophy, stem cell proliferation, PCNA, exercise-induced muscle damage
MeSH terms
Humans, Male, Muscle Contraction, Organ Size, Signal Transduction, Interleukin-6, Muscle, Skeletal, Satellite Cells, Skeletal Muscle, STAT3 Transcription Factor, Janus Kinase 2, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review