%0 Journal Article
%T Leu promotes C2C12 cell differentiation by regulating the GSK3β/β-catenin signaling pathway through facilitating the interaction between SESN2 and RPN2.
%A Liu Y
%A Li J
%A Ding C
%A Tong H
%A Yan Y
%A Li S
%A Li S
%A Cao Y
%J J Sci Food Agric
%V 104
%N 11
%D 2024 Aug 30
%M 38551359
%F 4.125
%R 10.1002/jsfa.13496
%X <B>BACKGROUND: </B>Leucine (Leu) is an essential amino acid that facilitates skeletal muscle satellite cell differentiation, yet its mechanism remains underexplored. Sestrin2 (SESN2) serves as a Leu sensor, binding directly to Leu, while ribophorin II (RPN2) acts as a signaling factor in multiple pathways. This study aimed to elucidate Leu's impact on mouse C2C12 cell differentiation and skeletal muscle injury repair by modulating RPN2 expression through SESN2, offering a theoretical foundation for clinical skeletal muscle injury prevention and treatment.<BR><B>RESULTS: </B>Leu addition promoted C2C12 cell differentiation compared to the control, enhancing early differentiation via myogenic determinant (MYOD) up-regulation. Sequencing revealed SESN2 binding to and interacting with RPN2. RPN2 overexpression up-regulated MYOD, myogenin and myosin heavy chain 2, concurrently decreased p-GSK3β and increased nuclear β-catenin. Conversely, RPN2 knockdown yielded opposite results. Combining RPN2 knockdown with Leu rescued increased p-GSK3β and decreased nuclear β-catenin compared to Leu absence. Hematoxylin and eosin staining results showed that Leu addition accelerated mouse muscle damage repair, up-regulating Pax7, MYOD and RPN2 in the cytoplasm, and nuclear β-catenin, confirming that the role of Leu in muscle injury repair was consistent with the results for C2C12 cells.<BR><B>CONCLUSIONS: </B>Leu, bound with SESN2, up-regulated RPN2 expression, activated the GSK3β/β-catenin pathway, enhanced C2C12 differentiation and expedited skeletal muscle damage repair. © 2024 Society of Chemical Industry.