Molecular signatures of differential responses to exercise trainings during rehabilitation
Abstract
The loss and recovery of muscle mass and function following injury and during rehabilitation varies among individuals. While recent expression profiling studies have illustrated transcriptomic responses to muscle disuse and remodeling, how these changes contribute to the physiological responses are not clear. In this study, we quantified the effects of immobilization and subsequent rehabilitation training on muscle size and identified molecular pathways associated with muscle responsiveness in an orthopaedic patient cohort study. The injured leg of 16 individuals with ankle injury was immobilized for a minimum of 4 weeks, followed by a 6-week rehabilitation program. The maximal cross-sectional area (CSA) of the medial gastrocnemius muscle of the immobilized and control legs were determined by T1-weighted axial MRI images. Genome-wide mRNA profiling data were used to identify molecular signatures that distinguish the patients who responded to immobilization and rehabilitation and those who were considered minimal responders. RESULTS: Using 6% change as the threshold to define responsiveness, a greater degree of changes in muscle size was noted in high responders (-14.9 ± 3.6%) compared to low responders (0.1 ± 0.0%) during immobilization. In addition, a greater degree of changes in muscle size was observed in high responders (20.5 ± 3.2%) compared to low responders (2.5 ± 0.9%) at 6-week rehabilitation. Microarray analysis showed a higher number of genes differentially expressed in the responders compared to low responders in general; with more expression changes observed at the acute stage of rehabilitation in both groups. Pathways analysis revealed top molecular pathways differentially affected in the groups, including genes involved in mitochondrial function, protein turn over, integrin signaling and inflammation. This study confirmed the extent of muscle atrophy due to immobilization and recovery by exercise training is associated with distinct remodeling signature, which can potentially be used for evaluating and predicting clinical outcomes.
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BibTeX
@article{chen2026molecular,
title = {{Molecular signatures of differential responses to exercise trainings during rehabilitation}},
author = {Yi-Wen Chen and Chris Gregory and Fan Ye and Naoe Harafuji and Donovan Lott and San-Huei Lai and Sunita Mathur and Mark Scarborough and Parker Gibbs and Celine Baligand and Krista Vandenborne},
journal = {Biomedical Genetics and Genomics},
year = {2026},
month = oct,
doi = {10.15761/bgg.1000127},
url = {https://hal.science/hal-05780243v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Molecular signatures of differential responses to exercise trainings during rehabilitation
AU - Yi-Wen Chen
AU - Chris Gregory
AU - Fan Ye
AU - Naoe Harafuji
AU - Donovan Lott
AU - San-Huei Lai
AU - Sunita Mathur
AU - Mark Scarborough
AU - Parker Gibbs
AU - Celine Baligand
AU - Krista Vandenborne
PY - 2026
DA - 2026/10/06
JO - Biomedical Genetics and Genomics
DO - 10.15761/bgg.1000127
UR - https://hal.science/hal-05780243v1
AB - The loss and recovery of muscle mass and function following injury and during rehabilitation varies among individuals. While recent expression profiling studies have illustrated transcriptomic responses to muscle disuse and remodeling, how these changes contribute to the physiological responses are not clear. In this study, we quantified the effects of immobilization and subsequent rehabilitation training on muscle size and identified molecular pathways associated with muscle responsiveness in an orthopaedic patient cohort study. The injured leg of 16 individuals with ankle injury was immobilized for a minimum of 4 weeks, followed by a 6-week rehabilitation program. The maximal cross-sectional area (CSA) of the medial gastrocnemius muscle of the immobilized and control legs were determined by T1-weighted axial MRI images. Genome-wide mRNA profiling data were used to identify molecular signatures that distinguish the patients who responded to immobilization and rehabilitation and those who were considered minimal responders. RESULTS: Using 6% change as the threshold to define responsiveness, a greater degree of changes in muscle size was noted in high responders (-14.9 ± 3.6%) compared to low responders (0.1 ± 0.0%) during immobilization. In addition, a greater degree of changes in muscle size was observed in high responders (20.5 ± 3.2%) compared to low responders (2.5 ± 0.9%) at 6-week rehabilitation. Microarray analysis showed a higher number of genes differentially expressed in the responders compared to low responders in general; with more expression changes observed at the acute stage of rehabilitation in both groups. Pathways analysis revealed top molecular pathways differentially affected in the groups, including genes involved in mitochondrial function, protein turn over, integrin signaling and inflammation. This study confirmed the extent of muscle atrophy due to immobilization and recovery by exercise training is associated with distinct remodeling signature, which can potentially be used for evaluating and predicting clinical outcomes.
SN - 2398-5399
SN - 2398-5399
ER -