NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration

• Published in: Biological research Vol. 56; no. 1; p. 21
• Main Authors: Cabezas, Felipe, Cabello-Verrugio, Claudio, González, Natalia, Salas, Jeremy, Ramírez, Manuel J, de la Vega, Eduardo, Olguín, Hugo C
• Format: Journal Article
• Language: English; Portuguese
• Published: England BioMed Central Ltd 05.05.2023; BioMed Central; Sociedad de Biología de Chile; BMC
• Subjects: BIOLOGY; Cell Differentiation; Cell Proliferation - physiology; Enzymes; Fibroblasts; Homeostasis; Ligases; Muscle Development - physiology; Muscle differentiation; Muscle stem cells; Muscle, Skeletal - metabolism; Muscles; Musculoskeletal system; NEDD4-1; PAX7 Transcription Factor - genetics; PAX7 Transcription Factor - metabolism; Proteasome Endopeptidase Complex - metabolism; Proteasomes; Proteins; Satellite cells; Skeletal muscle; Skeletal muscle regeneration; Stem Cells; Ubiquitin; Ubiquitin-protein ligase; Ubiquitins - metabolism; Germany; Skeletal muscle regeneration; Satellite cells; NEDD4-1; Muscle differentiation; Muscle stem cells
• ISSN: 0717-6287; 0716-9760; 0717-6287
• DOI: 10.1186/s40659-023-00432-7

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. 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. 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.