Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury
Abstract 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, coordin...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-02-01
|
| Series: | Genome Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13073-025-01434-8 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1823861735743815680 |
|---|---|
| author | Ren Zhou Jibao Chen Yunhan Tang Chuijin Wei Ping Yu Xinmei Ding Li’ao Zhu Jiajia Yao Zengqiang Ouyang Jing Qiao Shumin Xiong Liaoliao Dong Tong Yin Haiqing Li Ye Feng Lin Cheng |
| author_facet | Ren Zhou Jibao Chen Yunhan Tang Chuijin Wei Ping Yu Xinmei Ding Li’ao Zhu Jiajia Yao Zengqiang Ouyang Jing Qiao Shumin Xiong Liaoliao Dong Tong Yin Haiqing Li Ye Feng Lin Cheng |
| author_sort | Ren Zhou |
| collection | DOAJ |
| description | Abstract 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 locomotor function following SCI in the human trial. Moreover, it was emphasized that resistance exercise interventions could effectively modulate these pathways. Through employing plasma proteomic profiling and transcriptomic profiling of PBMC and muscle tissues in mice, our study revealed immunomodulatory responses that parallel those observed in human trials. In addition, our analysis of plasma metabolomics revealed an enhancement in lipid metabolism following resistance exercise. We observed that resistance exercise plasma exhibited significant effects in ameliorating locomotor disability after SCI via reducing demyelination and inhibiting neuronal apoptosis. Conclusions Our investigation elucidates the molecular alterations associated with resistance exercise therapy promoting recovery of locomotor function following incomplete SCI. Moreover, we demonstrate the direct neuroprotective effects delivered via exercise plasma injection, which facilitates spinal cord repair. Mechanistically, the comprehensive multi-omics analysis involving both human and mice reveals that the principal constituents responsible for the observed neuroprotective effects within the plasma are predominantly immunoregulatory factors, warranting further experimental validation. Trial registration The study was retrospectively registered on 17 July, 2024, in Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at https://www.chictr.org.cn/ . |
| format | Article |
| id | doaj-art-838e3d28316d42199a2417d8b4f30509 |
| institution | Kabale University |
| issn | 1756-994X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj-art-838e3d28316d42199a2417d8b4f305092025-02-09T12:48:41ZengBMCGenome Medicine1756-994X2025-02-0117112510.1186/s13073-025-01434-8Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injuryRen Zhou0Jibao Chen1Yunhan Tang2Chuijin Wei3Ping Yu4Xinmei Ding5Li’ao Zhu6Jiajia Yao7Zengqiang Ouyang8Jing Qiao9Shumin Xiong10Liaoliao Dong11Tong Yin12Haiqing Li13Ye Feng14Lin Cheng15Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of General Medicine, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Emergency, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of MedicineDepartment of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Cardiac Surgery, Ruijin Hospital, Shanghai Jiaotong University School of MedicineDepartment of Neurology and Neurological Rehabilitation, Shanghai YangZhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), Tongji University School of MedicineShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of MedicineAbstract 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 locomotor function following SCI in the human trial. Moreover, it was emphasized that resistance exercise interventions could effectively modulate these pathways. Through employing plasma proteomic profiling and transcriptomic profiling of PBMC and muscle tissues in mice, our study revealed immunomodulatory responses that parallel those observed in human trials. In addition, our analysis of plasma metabolomics revealed an enhancement in lipid metabolism following resistance exercise. We observed that resistance exercise plasma exhibited significant effects in ameliorating locomotor disability after SCI via reducing demyelination and inhibiting neuronal apoptosis. Conclusions Our investigation elucidates the molecular alterations associated with resistance exercise therapy promoting recovery of locomotor function following incomplete SCI. Moreover, we demonstrate the direct neuroprotective effects delivered via exercise plasma injection, which facilitates spinal cord repair. Mechanistically, the comprehensive multi-omics analysis involving both human and mice reveals that the principal constituents responsible for the observed neuroprotective effects within the plasma are predominantly immunoregulatory factors, warranting further experimental validation. Trial registration The study was retrospectively registered on 17 July, 2024, in Chinese Clinical Trial Registry (No.: ChiCTR2400087038) at https://www.chictr.org.cn/ .https://doi.org/10.1186/s13073-025-01434-8Resistance exerciseMulti-omicsProteomeMetabolomeSpinal cord injuryNeuroprotection |
| spellingShingle | Ren Zhou Jibao Chen Yunhan Tang Chuijin Wei Ping Yu Xinmei Ding Li’ao Zhu Jiajia Yao Zengqiang Ouyang Jing Qiao Shumin Xiong Liaoliao Dong Tong Yin Haiqing Li Ye Feng Lin Cheng Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury Genome Medicine Resistance exercise Multi-omics Proteome Metabolome Spinal cord injury Neuroprotection |
| title | Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury |
| title_full | Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury |
| title_fullStr | Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury |
| title_full_unstemmed | Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury |
| title_short | Multi-omics uncovers immune-modulatory molecules in plasma contributing to resistance exercise-ameliorated locomotor disability after incomplete spinal cord injury |
| title_sort | multi omics uncovers immune modulatory molecules in plasma contributing to resistance exercise ameliorated locomotor disability after incomplete spinal cord injury |
| topic | Resistance exercise Multi-omics Proteome Metabolome Spinal cord injury Neuroprotection |
| url | https://doi.org/10.1186/s13073-025-01434-8 |
| work_keys_str_mv | AT renzhou multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT jibaochen multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT yunhantang multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT chuijinwei multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT pingyu multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT xinmeiding multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT liaozhu multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT jiajiayao multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT zengqiangouyang multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT jingqiao multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT shuminxiong multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT liaoliaodong multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT tongyin multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT haiqingli multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT yefeng multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury AT lincheng multiomicsuncoversimmunemodulatorymoleculesinplasmacontributingtoresistanceexerciseamelioratedlocomotordisabilityafterincompletespinalcordinjury |