Mustn1 is a smooth muscle cell-secreted microprotein that modulates skeletal muscle extracellular matrix composition

• DOI: 10.1016/j.molmet.2024.101912
• Publication Date: 2024-03-06T16:50:00Z
• Authors: Serge Ducommun; Paulo R. Jannig; Igor Cervenka; Marta Murgia; Melanie J. Mitten...; Ekaterina Chernog...; José M. Dias; Baptiste Jude; Jorge C. Correia; Jonathan G. Van V...; Gabriel Ocana-San...; Margareta Porsmyr...; Sarah McCann Haworth; Vicente Martínez-...; Zhengye Liu; Mattias Carlström; Matthias Mann; Johanna T. Lanner; Ana I. Teixeira; Lars Maegdefessel; Bruce M. Spiegelman; Jorge L. Ruas
• Keywords: Myocytes; 0303 health sciences; Leiokine; Extracellular Matrix/metabolism; Extracellular matrix; Skeletal/metabolism; RC31-1245; Muscular Atrophy/metabolism; Microprotein; Mice; 03 medical and health sciences; Hypertrophy/metabolism; Smooth muscle; Muscle regeneration; Mustn1; Animals; Humans; Muscle; Female; Original Article; Micropeptides; Internal medicine; Smooth Muscle/metabolism

Skeletal muscle plasticity and remodeling are critical for adapting tissue function to use, disuse, regeneration. The aim of this study was identify genes molecular pathways that regulate the transition from atrophy compensatory hypertrophy or recovery injury. Here, we have used a mouse model hindlimb unloading reloading, which causes skeletal atrophy, regeneration hypertrophy, respectively. We analyzed at reloading changes in transcriptome extracellular fluid proteome. then qRT-PCR, immunohistochemistry, bulk single-cell RNA sequencing data determine Mustn1 gene protein expression, including expression human with different challenges such as exercise generated Mustn1-deficient genetic models characterized them vivo ex regard whole-body metabolism. isolated smooth cells functionally them, performed transcriptomics proteomics analysis aorta mice. show (Musculoskeletal embryonic nuclear 1, also known Mustang) is highly expressed during early stages reloading. transiently elevated response intense exercise, resistance find highest muscle-rich tissues, followed by fibers. Muscle heterozygous mice exhibit differences related matrix cell adhesion, compared wild-type littermates. normal glucose Loss vascular does not affect their proliferative migratory functions. can be secreted cells, it present arterioles microvasculature fluid, particularly phase. Proteomics confirms composition, female display higher collagen content after chemically induced injury that, addition its previously reported intracellular localization, microprotein into space. explore role ECM deposition homeostasis upon fibrosis immune infiltration dystrophies remains investigated, potential therapeutic interventions.