Integrative bioinformatic analysis identifies an extracellular matrix gene signature linked to muscle adaptation to endurance and resistance training.

Skeletal muscle exhibits a remarkable adaptive capacity; endurance training enhances mitochondrial capacity, whereas resistance training improves mechanical strength. Despite these differences, both training impose repeated contractile and remodeling demands on skeletal muscle, suggesting a conserved transcriptional response that may underpin the muscle's capacity to endure long-term training. However, a systematic analysis of the universal gene signature common to both training types has not yet been conducted. We therefore reanalyzed microarray datasets from human skeletal muscle samples obtained before and after endurance and resistance training. We first identified differentially expressed genes in each dataset, then performed a cross-dataset comparison to determine reproducible transcriptional responses across heterogeneous training protocols. Our results identified extracellular matrix (ECM) remodeling-related genes as conserved transcriptional responses to both endurance and resistance training. Moreover, we observed modality-associated gene signatures: endurance training was associated with ECM-adhesion and matrix connectivity, whereas resistance training preferentially promoted ECM structural maturation and reinforcement. These findings suggest that ECM-centered transcriptional regulation is a conserved and reproducible feature of skeletal muscle responses to both endurance and resistance training. The central role of ECM remodeling in the plasticity of human skeletal muscle establishes a comprehensive framework for future mechanistic investigations into how exercise induces cellular adaptations.