Skeletal muscle adaptations following eccentric contractions are not mediated by keratin 18.

The molecular mechanisms that drive muscle adaptations after eccentric exercise training are multifaceted and likely impacted by age. Previous studies have reported that many genes and proteins respond differently in young and older muscles following training. Keratin 18 (Krt18), a cytoskeletal protein involved in force transduction and organization, was found to be upregulated after muscles performed repeated bouts of eccentric contractions, with higher levels observed in young muscle compared with older muscle. Therefore, the purpose of this study was to determine if Krt18 mediates skeletal muscle adaptations following eccentric exercise training. The anterior crural muscles of Krt18 knockout (KO) and wild-type (WT) mice were subjected to either a single bout or repeated bouts of eccentric contractions, with isometric torque assessed across the initial and final bouts. Functionally, Krt18 KO and WT mice did not differ prior to performing any eccentric contractions ( ≥ 0.100). Muscle strength (tetanic isometric torques) and the ability to adapt to eccentric exercise training were also consistent across strains at all time points ( ≥ 0.169). Stated differently, immediate strength deficits and the recovery of strength following a single bout or multiple bouts of eccentric contractions were similar between Krt18 KO and WT mice. In summary, the absence of Krt18 does not impede the muscle's ability to adapt to repeated eccentric contractions, suggesting it is not essential for exercise-induced remodeling. The molecular processes that underlie the changes in skeletal muscle following eccentric exercise training are complex and involve multiple factors. Our findings indicate that Krt18 may not play a significant role in muscle adaptations following eccentric exercise training, likely due to its low expression in skeletal muscle. These results underscore the complexity of the molecular mechanisms that contribute to muscle plasticity and highlight the need for further research in this area.