The titin N2A-MARP signalosome constrains muscle longitudinal hypertrophy in response to stretch.

ABSTRACT: Titin-based mechanosensing is a key driver of trophic signaling in muscle, yet the downstream pathways linking titin sensing to muscle remodeling remain poorly understood. To investigate these signaling mechanisms, we utilized unilateral diaphragm denervation (UDD), an in vivo model that induces titin-stiffness-dependent hypertrophy via mechanical stretch. Using UDD in rats and mice, we characterized the longitudinal hypertrophic response and distinguished stretch-induced signaling from denervation effects by performing global transcriptomic and proteomic analyses following UDD and bilateral diaphragm denervation (BDD) in rats. Our findings identified upregulation of titin-associated muscle ankyrin repeat proteins (MARPs). Subsequent phosphorylation enrichment mass spectrometry in mouse di

SUBMITTER: van der Pijl R 

PROVIDER: S-EPMC12262232 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature