Overexpression of Mechano-Growth Factor Modulates Inflammatory Cytokine Expression and Macrophage Resolution in Skeletal Muscle Injury.

Sun KT, Cheung KK, Au SWN, Yeung SS, Yeung EW

Frontiers in physiology26 Jul 2018Cited by 11 (Europe PMC)

PMID30140235PMCIDPMC6094977DOI10.3389/fphys.2018.00999PepBankPUB-30140235

Summary

In muscle regeneration, infiltrating myeloid cells, such as macrophages mediate muscle inflammation by releasing key soluble factors. One such factor, insulin-like growth factor 1 (IGF-1), suppresses inflammatory cytokine expression and mediates macrophage polarization to anti-inflammatory phenotype during muscle injury. Previously the IGF-1Ea isoform was shown to be anti-inflammatory. Another isoform of IGF-1, mechano-growth factor (MGF), is structurally and functionally distinct from IGF-1Ea, but its role in muscle inflammation has not yet been characterized. In this study, we hypothesized that MGF expression in muscle injury modulates muscle inflammation. We first investigated changes of transcription and expression of MGF in response to skeletal muscle injury induced by cardiotoxin (CTX) in vivo. At 1-2 days post-injury, Mgf expression was significantly upregulated and positively correlated with that of inflammatory cytokines. Immunostaining revealed that infiltration of neutrophils and macrophages coincided with Mgf upregulation. Furthermore, infiltrating neutrophils and macrophages expressed Mgf, suggesting their contribution to MGF upregulation in muscle injury. Macrophages seem to be the predominant source of MGF in muscle injury, whereas neutrophil depletion did not affect muscle Mgf expression. Given the association of MGF and macrophages, we then studied whether MGF could affect macrophage infiltration and polarization. To test this, we overexpressed MGF in CTX-injured muscles and evaluated inflammatory marker expression, macrophage populations, and muscle regeneration outcomes. MGF overexpression delayed the resolution of macrophages, particularly the pro-inflammatory phenotype. This coincided with upregulation of inflammatory markers. Annexin V-based flow cytometry revealed that MGF overexpression likely delays macrophage resolution by limiting macrophage apoptosis. Although MGF overexpression did not obviously affect muscle regeneration outcomes, the findings are novel and provide insights on the physiological roles of MGF in muscle regeneration.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

No result from this study comes from a test of the peptide.

Natural levels measured5

These results measure the body's own peptide. Nobody was given the peptide. They are not evidence about taking it. They are left out of key results, evidence counts and charts.

01AnimalEndogenous levelAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, Mgf expression was significantly upregulated at 1-2 days post-injury and correlated positively with inflammatory cytokines.
In plain wordsIn animals with muscle injury, the body's own Mgf rose in the first 1-2 days and tracked with inflammation markers.
Peptide
MGF / PEG-MGF
Outcome
IncreaseMgf expression after muscle injury
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
At 1-2 days post-injury, Mgf expression was significantly upregulated and positively correlated with that of inflammatory cytokines.
1 context sentence(design, population, supporting numbers)
Summary · context
We first investigated changes of transcription and expression of MGF in response to skeletal muscle injury induced by cardiotoxin (CTX) in vivo.
This result measures the body's own MGF / PEG-MGF. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3014023501
02AnimalEndogenous levelAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, infiltrating neutrophils and macrophages expressed Mgf.
In plain wordsIn animals with muscle injury, immune cells that entered the muscle made the body's own Mgf.
Peptide
MGF / PEG-MGF
Outcome
Not applicableSource of Mgf in injured muscle
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
Furthermore, infiltrating neutrophils and macrophages expressed Mgf, suggesting their contribution to MGF upregulation in muscle injury.
1 context sentence(design, population, supporting numbers)
Summary · context
We first investigated changes of transcription and expression of MGF in response to skeletal muscle injury induced by cardiotoxin (CTX) in vivo.
This result measures the body's own MGF / PEG-MGF. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3014023502
03AnimalEndogenous levelAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, neutrophil depletion did not affect muscle Mgf expression.
In plain wordsIn animals with muscle injury, removing neutrophils did not change the body's own Mgf level in muscle.
Peptide
MGF / PEG-MGF
Outcome
No significant changeMuscle Mgf expression after neutrophil depletion
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
whereas neutrophil depletion did not affect muscle Mgf expression.
1 context sentence(design, population, supporting numbers)
Summary · context
We first investigated changes of transcription and expression of MGF in response to skeletal muscle injury induced by cardiotoxin (CTX) in vivo.
This result measures the body's own MGF / PEG-MGF. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3014023503
04AnimalEndogenous levelAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, infiltration of neutrophils and macrophages coincided with upregulation of Mgf.
In plain wordsIn animals with muscle injury, immune cells entered the muscle at the same time as the body's own Mgf rose.
Peptide
MGF / PEG-MGF
Outcome
Not applicableInfiltration of neutrophils and macrophages alongside Mgf upregulation
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
Immunostaining revealed that infiltration of neutrophils and macrophages coincided with Mgf upregulation.
This result measures the body's own MGF / PEG-MGF. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3014023508
05AnimalEndogenous levelAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, macrophages seemed to be the predominant source of Mgf.
In plain wordsIn animals with muscle injury, macrophages seemed to be the main makers of the body's own Mgf in muscle.
Peptide
MGF / PEG-MGF
Outcome
Not applicablePredominant source of Mgf in muscle injury
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
Macrophages seem to be the predominant source of MGF in muscle injury
This result measures the body's own MGF / PEG-MGF. Nobody was given the peptide. It is not evidence about taking it.
Show in the study text Report a problemFND-3014023509

Studies that did not test the peptide alone4

In this study, MGF / PEG-MGF was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking MGF / PEG-MGF.

06AnimalNot a test of MGF / PEG-MGF aloneAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, MGF overexpression delayed the resolution of macrophages, particularly the pro-inflammatory phenotype.
In plain wordsIn animals with muscle injury, forced extra MGF production slowed the clearing of inflammatory immune cells.
Peptide
MGF / PEG-MGF
Outcome
DecreaseMacrophage resolution with MGF overexpression
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
MGF overexpression delayed the resolution of macrophages, particularly the pro-inflammatory phenotype.
1 context sentence(design, population, supporting numbers)
Summary · context
To test this, we overexpressed MGF in CTX-injured muscles and evaluated inflammatory marker expression, macrophage populations, and muscle regeneration outcomes.
In this study, MGF / PEG-MGF was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MGF / PEG-MGF.
Show in the study text Report a problemFND-3014023504
07AnimalNot a test of MGF / PEG-MGF aloneAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, MGF overexpression coincided with upregulation of inflammatory markers.
In plain wordsIn animals with muscle injury, forced extra MGF production came with higher inflammation markers.
Peptide
MGF / PEG-MGF
Outcome
IncreaseInflammatory marker expression with MGF overexpression
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
This coincided with upregulation of inflammatory markers.
1 context sentence(design, population, supporting numbers)
Summary · context
To test this, we overexpressed MGF in CTX-injured muscles and evaluated inflammatory marker expression, macrophage populations, and muscle regeneration outcomes.
In this study, MGF / PEG-MGF was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MGF / PEG-MGF.
Show in the study text Report a problemFND-3014023505
08AnimalNot a test of MGF / PEG-MGF aloneAnimal study (in vivo)Mechanism
In cardiotoxin-injured muscle, MGF overexpression likely delayed macrophage resolution by limiting macrophage apoptosis.
In plain wordsIn animals with muscle injury, forced extra MGF production likely slowed macrophage clearing by limiting their cell death.
Peptide
MGF / PEG-MGF
Outcome
DecreaseMacrophage apoptosis with MGF overexpression
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
Annexin V-based flow cytometry revealed that MGF overexpression likely delays macrophage resolution by limiting macrophage apoptosis.
1 context sentence(design, population, supporting numbers)
Summary · context
To test this, we overexpressed MGF in CTX-injured muscles and evaluated inflammatory marker expression, macrophage populations, and muscle regeneration outcomes.
In this study, MGF / PEG-MGF was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MGF / PEG-MGF.
Show in the study text Report a problemFND-3014023506
09AnimalNot a test of MGF / PEG-MGF aloneAnimal study (in vivo)Efficacy outcome
In cardiotoxin-injured muscle, MGF overexpression did not obviously affect muscle regeneration outcomes.
In plain wordsIn animals with muscle injury, forced extra MGF production did not clearly change muscle recovery.
Peptide
MGF / PEG-MGF
Outcome
No significant changeMuscle regeneration outcomes with MGF overexpression
Study
n: not reported in source
cardiotoxin-induced skeletal muscle injury
Outcome group
Muscle injury and repair · Musculoskeletal
Source sentences
Summary
MGF overexpression did not obviously affect muscle regeneration outcomes, the findings are novel and provide insights on the physiological roles of MGF in muscle regeneration.
1 context sentence(design, population, supporting numbers)
Summary · context
To test this, we overexpressed MGF in CTX-injured muscles and evaluated inflammatory marker expression, macrophage populations, and muscle regeneration outcomes.
In this study, MGF / PEG-MGF was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking MGF / PEG-MGF.
Show in the study text Report a problemFND-3014023507

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

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