CXCL14 Promotes Skeletal Muscle Mass Growth and Attenuates Lipopolysaccharide- and Dexamethasone-Induced Muscle Atrophy in Cultured Myotubes and Mouse Models.
Level 5 - mechanism / opinion, no new human data
Preclinical animal and in vitro cell culture study without human clinical trial data
PubMed 41085163 · doi:10.1002/jcsm.70087
What was done
Researchers evaluated the role of CXCL14 on skeletal muscle mass using C2C12 mouse myotubes, primary human myotubes, and 8-week-old male mice (ICR and C57BL/6N strains). In vitro cultures were treated with recombinant CXCL14 alone or in combination with Rps6kb1 siRNA, lipopolysaccharide (LPS), or dexamethasone (DEX), measuring the myotube mass index (MMI) and pathway markers via Western blotting. In vivo, Cxcl14 expression plasmids were delivered into tibialis anterior (TA) muscles via electroporation with or without LPS- or DEX-induced atrophy models. Muscle fiber cross-sectional area (CSA), Western blotting, and RNA sequencing were evaluated.
What was found
In C2C12 myotubes, 100 ng/mL CXCL14 increased MMI to 1345 ± 50.97 μm² (95% CI: 1237–1453) compared to 897.9 ± 33.33 μm² in controls (95% CI: 829.8–996; p ≤ 0.0001). In primary human myotubes, 100 ng/mL CXCL14 increased MMI to 3481 ± 242.6 μm² (95% CI: 2973–3989) compared to 2549 ± 114.7 μm² in controls (95% CI: 2310–2787; p ≤ 0.001). In mouse TA muscle, Cxcl14 overexpression increased CSA to 1408 ± 15.42 μm² (HA-CXCL14) and 1499 ± 17.18 μm² (CXCL14-Myc) compared to control (870.1 ± 11.25 μm²; p ≤ 0.0001). CXCL14 significantly attenuated LPS- and DEX-induced atrophy in all models (p ≤ 0.01 to p ≤ 0.0001), associated with activation of the AKT-S6K pathway and inhibition of the FOXO-Atrogin-1/MuRF-1 pathway.
Why it matters
These findings suggest that CXCL14 acts as an anabolic and anti-catabolic factor in skeletal muscle. This identifies a potential mechanistic target for interventions aimed at mitigating muscle wasting from inflammatory or glucocorticoid-induced cachexia and sarcopenia.
Limits
The study is restricted to in vitro and mouse models, and total animal/sample counts (n) are not specified in the abstract. Whether local overexpression or recombinant delivery translates to safe, systemic, and durable efficacy in human disease states remains untested.
Cited by
- supports Lipopolysaccharide (LPS) administration causes extensive muscle wasting and sarcopenia over time in experimental models.