Vitamin D binding protein induces skeletal muscle atrophy and contributes to cancer-associated muscle wasting

ABSTRACT: The maintenance of skeletal muscle tissue is of pivotal importance in health and disease, as its loss is often associated with chronic or progressive pathologies, generally worsening the prognosis. Increased levels of vitamin D binding protein (VDBP) in biological samples were reported to co-occur with several pathologies susceptible to muscle wasting, including various types of tumors. We, therefore, hypothesized that VDBP may participate in muscle wasting and investigated its direct effects on skeletal muscle homeostasis. Here we demonstrate that VDBP induces atrophy independently of vitamin D. In C2C12 myotubes, we identified the perturbation of the intracellular actin dynamic and subsequent mitochondrial dysfunction as the main molecular mechanisms at the basis of VDBP-induced atrophy. Coherently, the ectopic introduction of VDBP in mice lacking the protein (Gc-knockout mice; Gc-KO) induces muscle atrophy, the dismantling of neuromuscular junctions, and decreased force. Finally, we provide proof-of-concept evidence that VDBP contributes to cancer-associated muscle wasting. Altogether, these findings provide novel insights into the biological function of VDBP and have potential implications for the treatment of muscle wasting.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: Marcello Manfredi  

LAB HEAD: Marcello Manfredi

PROVIDER: PXD042024 | Pride | 2026-02-20

REPOSITORIES: Pride