CXCL14 Promotes Skeletal Muscle Mass Growth and Attenuates Lipopolysaccharide- and Dexamethasone-Induced Muscle Atrophy in Cultured Myotubes and Mouse Models.

backgroundSkeletal 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.

methodsThis 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.

resultsCXCL14 induced hypertrophy in C2C12-derived myotubes: (MMI [μm

conclusionsOur 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.