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Study · In vitro (cells) · 2026

9 results

Mitochondrial-derived peptides MOTS-c and humanin attenuate dexamethasone-induced atrophy in human skeletal muscle cells.

Elhusseiny R, Ihsan M, Bellefroid T, Farooq A, Racinais S, Deldicque L

Physiological reports1 Feb 2026Cited by 1 (Europe PMC)

Summary

Glucocorticoids, such as dexamethasone (DEXA), are effective therapeutics but cause severe muscle wasting. Mitochondrial-derived peptides (MDPs) are promising countermeasures, but their effectiveness is largely unexplored. We tested the hypothesis that the MDP S14G-humanin (HNG) and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) mitigate DEXA-induced atrophy in human skeletal myotubes. Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c. DEXA decreased myotube size (area, p < 0.001) and differentiation (Fusion Index, p = 0.05). Additionally, DEXA increased both muscle ring finger protein 1 (MURF1, p < 0.001) and muscle atrophy F-box (MAFbx, p = 0.01) as well as peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α, p < 0.001). MOTS-c co-treatment with DEXA completely preserved myotube area (p < 0.001) and fusion index (p = 0.02), increased Akt phosphorylation (p = 0.0015) and blunted both MURF1 upregulation (p = 0.03) and STAT3 activation (p = 0.005) compared to DEXA alone. HNG co-treatment with DEXA preserved myotube area (p < 0.001), blunted DEXA-induced STAT3 activation (p = 0.027), but had no effect on fusion index or E3 ligase mRNA levels. Those findings suggest that MOTS-c could be an effective inhibitor of glucocorticoid-induced atrophy in human muscle, not only through selective inhibition of MURF1 but also by enhancing Akt signaling and suppressing STAT3 activation.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study9

9 results from studies that gave the peptide. No result from this study comes from people.

  1. 01LabIn vitro (cells)Efficacy outcome

    In primary human myotubes, MOTS‑c co-treatment preserved myotube area during dexamethasone exposure compared with dexamethasone alone.

    In plain wordsIn human muscle cells, MOTS‑c kept cell size from shrinking under dexamethasone, compared with dexamethasone alone.

    Peptide
    MOTS-c
    Outcome
    IncreaseMyotube area under dexamethasone
    Study

    humann: not reported in source

    Primary human myotubes
    Comparator
    DEXA alone
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    MOTS-c co-treatment with DEXA completely preserved myotube area (p < 0.001) and fusion index (p = 0.02), increased Akt phosphorylation (p = 0.0015) and blunted both MURF1 upregulation (p = 0.03) and STAT3 activation (p = 0.005) compared to DEXA alone.
    1 context sentence
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  2. 02LabIn vitro (cells)Efficacy outcome

    In primary human myotubes, MOTS‑c co-treatment preserved the fusion index during dexamethasone exposure compared with dexamethasone alone.

    In plain wordsIn human muscle cells, MOTS‑c kept muscle cell fusion from falling under dexamethasone, compared with dexamethasone alone.

    Peptide
    MOTS-c
    Outcome
    IncreaseFusion index under dexamethasone
    Study

    humann: not reported in source

    Primary human myotubes
    Comparator
    DEXA alone
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    MOTS-c co-treatment with DEXA completely preserved myotube area (p < 0.001) and fusion index (p = 0.02), increased Akt phosphorylation (p = 0.0015) and blunted both MURF1 upregulation (p = 0.03) and STAT3 activation (p = 0.005) compared to DEXA alone.
    1 context sentence
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  3. 03LabIn vitro (cells)Mechanism

    In primary human myotubes, MOTS‑c co-treatment increased Akt phosphorylation compared with dexamethasone alone.

    In plain wordsIn human muscle cells, MOTS‑c increased Akt signalling compared with dexamethasone alone.

    Peptide
    MOTS-c
    Outcome
    IncreaseAkt phosphorylation
    Study

    humann: not reported in source

    Primary human myotubes
    Comparator
    DEXA alone
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    MOTS-c co-treatment with DEXA completely preserved myotube area (p < 0.001) and fusion index (p = 0.02), increased Akt phosphorylation (p = 0.0015) and blunted both MURF1 upregulation (p = 0.03) and STAT3 activation (p = 0.005) compared to DEXA alone.
    1 context sentence
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  4. 04LabIn vitro (cells)Mechanism

    In primary human myotubes, MOTS‑c co-treatment blunted dexamethasone-induced MURF1 upregulation compared with dexamethasone alone.

    In plain wordsIn human muscle cells, MOTS‑c reduced the rise of the muscle-breakdown protein MURF1 caused by dexamethasone.

    Peptide
    MOTS-c
    Outcome
    DecreaseMURF1 upregulation
    Study

    humann: not reported in source

    Primary human myotubes
    Comparator
    DEXA alone
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    MOTS-c co-treatment with DEXA completely preserved myotube area (p < 0.001) and fusion index (p = 0.02), increased Akt phosphorylation (p = 0.0015) and blunted both MURF1 upregulation (p = 0.03) and STAT3 activation (p = 0.005) compared to DEXA alone.
    1 context sentence
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  5. 05LabIn vitro (cells)Mechanism

    In primary human myotubes, MOTS‑c co-treatment blunted STAT3 activation compared with dexamethasone alone.

    In plain wordsIn human muscle cells, MOTS‑c reduced STAT3 activation compared with dexamethasone alone.

    Peptide
    MOTS-c
    Outcome
    DecreaseSTAT3 activation
    Study

    humann: not reported in source

    Primary human myotubes
    Comparator
    DEXA alone
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    MOTS-c co-treatment with DEXA completely preserved myotube area (p < 0.001) and fusion index (p = 0.02), increased Akt phosphorylation (p = 0.0015) and blunted both MURF1 upregulation (p = 0.03) and STAT3 activation (p = 0.005) compared to DEXA alone.
    1 context sentence
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  6. 06LabIn vitro (cells)Efficacy outcome

    In human myotubes exposed to dexamethasone, co-treatment with the humanin analogue HNG preserved myotube area compared with dexamethasone alone.

    In plain wordsIn lab-grown human muscle cells, a humanin analogue kept the cells larger when dexamethasone was present, compared with dexamethasone alone.

    Peptide
    Humanin
    Outcome
    IncreaseMyotube area with dexamethasone
    Study

    humann: not reported in source

    Primary human skeletal myotubes exposed to dexamethasone
    Comparator
    Dexamethasone alone
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    HNG co-treatment with DEXA preserved myotube area (p < 0.001), blunted DEXA-induced STAT3 activation (p = 0.027), but had no effect on fusion index or E3 ligase mRNA levels.
    2 context sentences
    Summary · context
    We tested the hypothesis that the MDP S14G-humanin (HNG) and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) mitigate DEXA-induced atrophy in human skeletal myotubes.
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  7. 07LabIn vitro (cells)Mechanism

    In human myotubes exposed to dexamethasone, HNG co-treatment blunted dexamethasone-induced STAT3 activation.

    In plain wordsIn lab-grown human muscle cells, a humanin analogue reduced the STAT3 activation that dexamethasone caused.

    Peptide
    Humanin
    Outcome
    DecreaseSTAT3 activation with dexamethasone
    Study

    humann: not reported in source

    Primary human skeletal myotubes exposed to dexamethasone
    Comparator
    Dexamethasone alone
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    HNG co-treatment with DEXA preserved myotube area (p < 0.001), blunted DEXA-induced STAT3 activation (p = 0.027), but had no effect on fusion index or E3 ligase mRNA levels.
    2 context sentences
    Summary · context
    We tested the hypothesis that the MDP S14G-humanin (HNG) and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) mitigate DEXA-induced atrophy in human skeletal myotubes.
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  8. 08LabIn vitro (cells)Efficacy outcome

    In human myotubes exposed to dexamethasone, HNG co-treatment had no effect on the fusion index.

    In plain wordsIn lab-grown human muscle cells, a humanin analogue did not change the fusion index in the presence of dexamethasone.

    Peptide
    Humanin
    Outcome
    No significant changeFusion index with dexamethasone
    Study

    humann: not reported in source

    Primary human skeletal myotubes exposed to dexamethasone
    Comparator
    Dexamethasone alone
    Outcome group
    Muscle injury and repair · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    HNG co-treatment with DEXA preserved myotube area (p < 0.001), blunted DEXA-induced STAT3 activation (p = 0.027), but had no effect on fusion index or E3 ligase mRNA levels.
    2 context sentences
    Summary · context
    We tested the hypothesis that the MDP S14G-humanin (HNG) and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) mitigate DEXA-induced atrophy in human skeletal myotubes.
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.
  9. 09LabIn vitro (cells)Mechanism

    In human myotubes exposed to dexamethasone, HNG co-treatment had no effect on E3 ligase mRNA levels.

    In plain wordsIn lab-grown human muscle cells, a humanin analogue did not change E3 ligase mRNA levels in the presence of dexamethasone.

    Peptide
    Humanin
    Outcome
    No significant changeE3 ligase mRNA levels (MURF1, MAFbx) with dexamethasone
    Study

    humann: not reported in source

    Primary human skeletal myotubes exposed to dexamethasone
    Comparator
    Dexamethasone alone
    Outcome group
    Receptor activity and mechanism · Musculoskeletal
    Studied dose
    10 μMAs given in this study (human).

    Source sentences

    Summary
    HNG co-treatment with DEXA preserved myotube area (p < 0.001), blunted DEXA-induced STAT3 activation (p = 0.027), but had no effect on fusion index or E3 ligase mRNA levels.
    2 context sentences
    Summary · context
    We tested the hypothesis that the MDP S14G-humanin (HNG) and the mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) mitigate DEXA-induced atrophy in human skeletal myotubes.
    Summary · context
    Fully differentiated primary human myotubes were exposed to 10 μM DEXA ±10 μM HNG or 10 μM MOTS-c.

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.

  1. Versions 4 to 18Current

    28 Oct 2026, 02:02 UTC

    The same notice was added 15 times, first on 13 Oct 2026, 21:44 UTC. The status did not change between them.

    Study results updated

  2. Version 3

    13 Oct 2026, 16:31 UTC

    Study data updated · source update from Europe PMC

  3. Version 2

    10 Oct 2026, 08:19 UTC

    Study results updated

  4. Version 1

    9 Oct 2026, 02:47 UTC

    First added · source update from Europe PMC

Subjects

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