Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury

作者：Ren Zhou, Jibao Chen, Yunhan Tang, Chuijin Wei, Ping Yu, Xinmei Ding, Li’ao Zhu, Jiajia Yao, Zengqiang Ouyang, Jing Qiao, Shu-Min Xiong, Liaoliao Dong, Tong Yin, Haiqing Li, Feng Ye, Lin Cheng · 发表于：Genome Medicine · 年份：2025 · DOI：10.1186/s13073-025-01434-8 · 被引用次数：11 · 研究领域：Spinal Cord Injury Research、Zebrafish Biomedical Research Applications、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND: Exercise rehabilitation therapy has garnered widespread recognition for its beneficial effects on the restoration of locomotor function in individuals with spinal cord injury (SCI). Notably, resistance exercise has demonstrated significant improvements in muscle strength, coordination, and overall functional recovery. However, to optimize clinical management and mimic exercise-like effects, it is imperative to obtain a comprehensive understanding of the molecular alterations that underlie these positive effects. METHODS: We conducted a randomized controlled clinical trial investigating the effects of resistance exercise therapy for incomplete SCI. We integrated the analysis of plasma proteomics and peripheral blood mononuclear cells (PBMC) transcriptomics to explore the molecular and cellular changes induced by resistance exercise. Subsequently, we established a weight-loaded ladder-climbing mouse model to mimic the physiological effects of resistance exercise, and we analyzed the plasma proteome and metabolome, as well as the transcriptomes of PBMC and muscle tissue. Lastly, to confirm the transmissibility of the neuroprotective effects induced by resistance exercise, we intravenously injected plasma obtained from exercised male mice into SCI female mice during the non-acute phase. RESULTS: Plasma proteomic and PBMC transcriptomic profiling underscored the notable involvement of the complement pathways and humoral immune response in the process of restoring locom...