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Updated: Jan 15, 2026
Adult and Embryonic Skeletal Muscle Microexplant Culture and Isolation of Skeletal Muscle Stem Cells
Published on: September 21, 2010
CXCL14 Promotes Skeletal Muscle Mass Growth and Attenuates Lipopolysaccharide- and Dexamethasone-Induced Muscle
Bagus Sarmito1,2, Younjeong Oh1,2, Nurkyz Alymkulova1,2
1Department of Integrated Biomedical Science, Graduate School, Soonchunhyang University, Cheonan, South Korea.
Background:
Skeletal muscle mass is regulated by secretory factors derived from myofibers and muscle-resident cells. Identifying these factors and understanding their mechanisms is critical for combating muscle wasting disorders. This experimental study investigates the role of CXCL14, a chemokine primarily secreted by fibro-adipogenic progenitors (FAPs) residing in muscle, in regulating muscle mass.
Methods:
This study was conducted at the Soonchunhyang Institute of Medi-bio Science (SIMS), South Korea, between August 2020 and June 2025. Mouse C2C12 myotubes and primary human myotubes were treated with recombinant CXCL14, with or without co-treatment using Rps6kb1 siRNA, lipopolysaccharide (LPS) or dexamethasone (DEX). Myotube mass index (MMI) was measured. Expression of AKT-S6 kinase (S6K), FOXO-Atrogin-1/MuRF-1 signalling components and myosin heavy chains (MyHCs) was assessed via Western blotting. Eight-week-old male mice were used: ICR mice for electroporation experiments and C57BL/6N strain for LPS and DEX atrophy models. Cxcl14 expression plasmids were electroporated into tibialis anterior (TA) muscles, with or without LPS or DEX treatment. Cross-sectional area (CSA) of myofibers was measured; Western blotting and RNA sequencing were used to analyse molecular responses. Statistical analyses included one-way ANOVA with Tukey's post hoc test, repeated-measures ANOVA with Dunnett's post hoc test, Kruskal-Wallis test with Dunn's post hoc test and unpaired Student's t-test, as appropriate.
Results:
CXCL14 induced hypertrophy in C2C12-derived myotubes: (MMI [μm2]: 100 ng/mL CXCL14, 1345 ± 50.97 [95% CI: 1237-1453], vs. control, 897.9 ± 33.33 [95% CI: 829.8-996], p ≤ 0.0001). Cxcl14 overexpression in mouse TA muscles significantly increased muscle mass: (CSA [μm2]: HA-CXCL14: 1408 ± 15.42 [95% CI: 1378-1438]; CXCL14-Myc: 1499 ± 17.18 [95% CI: 1464-1534]; control: 870.1 ± 11.25 [95% CI: 848.1-892.2], p ≤ 0.0001). CXCL14 activated the AKT-S6K pathway and inhibited the FOXO-Atrogin-1/MuRF-1 pathway in both in vitro and in vivo models. CXCL14 effectively reversed LPS- and DEX-induced atrophy in both C2C12 myotubes and TA muscles, as demonstrated by corresponding increases MMI and CSA (all p ≤ 0.0001). CXCL14 also promoted hypertrophy in primary human myotubes in vitro (MMI [μm2]: 100 ng/mL CXCL14, 3481 ± 242.6 [95% CI: 2973-3989] vs. control, 2549 ± 114.7 [95% CI: 2310-2787], p ≤ 0.001) and significantly reversed atrophy induced by LPS and DEX (p ≤ 0.01 to p ≤ 0.0001), accompanying the activation of protein synthesis and inhibition of protein degradation pathways.
Conclusions:
Our findings identify CXCL14 as a novel regulator of skeletal muscle mass and highlight its therapeutic potential in preventing or reversing muscle atrophy associated with ageing and diseases in humans.
Insights
CXCL14, a chemokine secreted by muscle cells, promotes skeletal muscle growth and combats muscle wasting. This study demonstrates its potential to reverse muscle atrophy caused by aging and disease.
Area of Science:
- Cell Biology
- Molecular Biology
- Physiology
Background:
- Skeletal muscle mass is influenced by factors from muscle cells and resident cells.
- Understanding these factors is crucial for addressing muscle wasting disorders.
- This study focuses on CXCL14, a chemokine secreted by fibro-adipogenic progenitors (FAPs), and its role in muscle mass regulation.
Purpose of the Study:
- To investigate the function of CXCL14 in regulating skeletal muscle mass.
- To determine if CXCL14 influences muscle hypertrophy and atrophy.
- To explore the molecular pathways involved in CXCL14-mediated muscle regulation.
Main Methods:
- Experiments were conducted using mouse C2C12 myotubes, primary human myotubes, and mouse models (ICR and C57BL/6N strains).
- Treatments included recombinant CXCL14, Rps6kb1 siRNA, lipopolysaccharide (LPS), and dexamethasone (DEX).
- Techniques employed were Western blotting, RNA sequencing, and muscle cross-sectional area (CSA) measurements.
Main Results:
- CXCL14 significantly increased myotube mass index (MMI) in vitro and muscle mass in vivo.
- Overexpression of CXCL14 in mouse tibialis anterior (TA) muscles led to increased CSA.
- CXCL14 activated the AKT-S6K pathway and inhibited the FOXO-Atrogin-1/MuRF-1 pathway, reversing LPS- and DEX-induced atrophy.
Conclusions:
- CXCL14 is identified as a novel regulator of skeletal muscle mass.
- CXCL14 demonstrates therapeutic potential for preventing or reversing muscle atrophy.
- Findings suggest CXCL14's relevance in age-related muscle loss and disease-associated conditions.
