Integrated genomic and proteomic analyses identify stimulus-dependent molecular changes associated with distinct modes of skeletal muscle atrophy

ABSTRACT: Skeletal muscle atrophy is a debilitating condition that occurs with aging and disease but the underlying mechanisms are incompletely understood. Previous work determined that common transcriptional changes occur in muscle during atrophy induced by different stimuli. However, whether this holds true at the proteome level remains largely unexplored. Here, we find that, contrary to this earlier model, distinct atrophic stimuli (corticosteroids, cancer, and aging) induce largely different mRNA and protein changes during muscle atrophy in mice. Moreover, there is widespread transcriptome-proteome disconnect. Consequently, atrophy markers (atrogenes) identified in earlier microarray-based studies do not emerge from these proteomic surveys as the most relevantly associated with atrophy in all conditions. Rather, we identify proteins that are distinctly modulated by different types of atrophy (herein defined as “atroproteins”) such as the myokine CCN1/Cyr61, which regulates myofiber type switching during sarcopenia. Altogether, these integrated analyses indicate that different catabolic stimuli induce muscle atrophy via largely distinct mechanisms.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle Tissue, Tibialis Anterior

DISEASE(S): Muscular Atrophy,Cachexia

SUBMITTER: Zuo-Fei Yuan  

LAB HEAD: Fabio Demontis

PROVIDER: PXD027464 | Pride | 2022-02-22

REPOSITORIES: Pride