%0 Journal Article
%T NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration.
%A Cabezas F
%A Cabello-Verrugio C
%A González N
%A Salas J
%A Ramírez MJ
%A de la Vega E
%A Olguín HC
%J Biol Res
%V 56
%N 1
%D 2023 May 5
%M 37147738
%F 7.634
%R 10.1186/s40659-023-00432-7
%X <B>BACKGROUND: </B>Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined.<BR><B>RESULTS: </B>Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter.<BR><B>CONCLUSIONS: </B>These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.