Tensin2 deficiency transiently accelerates early-phase regenerative myofiber growth following cardiotoxin-induced injury in mice.

Abstract

Tensin2 (TNS2) is a focal adhesion-associated protein that can negatively regulate insulin/insulin-like growth factor 1 (IGF-1) signaling, but its role in skeletal muscle regeneration remains unclear. To address this, we analyzed a TNS2-related immunoreactive signal detected with an anti-phospho-TNS2 (Tyr483) antibody during C2C12 myogenic differentiation and in a cardiotoxin (CTX)-induced tibialis anterior (TA) injury model, and assessed regeneration in Tns2^nph mutant mice. Under basal conditions, Tns2^nph mice showed no obvious abnormalities in muscle histology, myofiber size, or phosphorylation of Akt and p70 ribosomal protein S6 kinase (p70S6K), a canonical downstream effector of mTORC1 signaling, compared with wild-type (WT) mice, although the soleus muscle/body weight ratio was slightly increased. In C2C12 cells, the anti-phospho-TNS2 (Tyr483)-reactive signal was stronger during proliferation than during differentiation. In vivo, this signal increased transiently during the early phase of CTX-mediated regeneration. After injury, Tns2^nph mice showed a greater number of centrally nucleated fibers at day 4, larger myofibers at day 7, and a higher TA muscle/body weight ratio at day 15. In addition, phosphorylation of p70S6K was increased in regenerating muscle in Tns2^nph mice. These findings suggest that TNS2-related signaling may act as a context-dependent modulator of regenerative myofiber growth, possibly through augmented anabolic signaling during early regeneration.