K. Xu1, X. Yang1, T. Peng1, Y. Wang1, J. Pan1, C. Fu1, J. Li1, Y. Zheng1, L. He1, H. Tang1
1Guangzhou Women and Children's Medical Center, Rehabilitation Department, Guangzhou, China
Background: Botulinum neurotoxin A (BoNT-A) has been shown to be effective in relieving spasticity in children with cerebral palsy (CP), but the molecular mechanisms mediating the effect remains largely unclear.
Purpose: To reveal the changes of protein expression induced by BoNT-A and to clarify the molecular mechanisms of BoNT-A injection on muscle spasticity in children with CP using data-independent acquisition (DIA) mass spectrometry.
Methods: Protein expression was measured 3 months after BoNT-A injection, using DIA in serum samples from 30 children with CP and 30 controls. Then, Gene Ontology, Kyoto Encyclopedia of Genes enrichment and protein-protein interaction network analyses were investigated the biological function of differentially regulated proteins. Quantitative real-time PCR and Western blotting were utilized to validate the findings of DIA.
Results: We screened 404 proteins from serum, of which 69 proteins were differentially expressed in BoNT-A groups when compared with the control group. The 39 proteins were up-regulated and 30 proteins were down-regulated. Ontological analysis revealed that 10 identified proteins (eg:Creatine kinase M-type, Myosin light polypeptide 6, Titin, et al.) were associated with alterations in muscle contractile function, transcription and cell proliferation. And those proteins activated the PI3K-Akt signaling pathway, which impacts the growth or atrophy of muscles.
Conclusion(s): This study provides comprehensive information about the protein changes in children with CP after receiving BoNT-A injection. The BoNT-A regulates various effector molecules and actives signaling pathways to regulate numerous cellular responses and affect the growth of muscles.
Implications: Our finding could provide a theoretical basis for explaining the beneficial or side effects of BoNT-A injection on the growth of muscle spasticity in children with CP in clinical application.
Funding, acknowledgements: National Natural Science Foundation of China(81902309, 81672253); Natural Science Foundation of Guangdong Province(2019A1515010420); Featured Clinical Technique of Guangzhou(2019TS55).
Keywords: BOTULINUM NEUROTOXIN A, SPASTICITY, CEREBRAL PALSY
Topic: Paediatrics: cerebral palsy
Did this work require ethics approval? Yes
Institution: Guangzhou Women and Children's Medical Center
Committee: Ethics Committee of Guangzhou Women and Children's Medical Center
Ethics number: 2020-23401
All authors, affiliations and abstracts have been published as submitted.
