Department of Rehabilitation, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Sport Rehabilitation, Shanghai University of Sport, shanghai, China.
Proteomics Clin Appl. 2024 Sep;18(5):e2300070. doi: 10.1002/prca.202300070. Epub 2024 Mar 8.
The study aims to explore the proteomic profile and specific target proteins associated with muscle growth in response to botulinum neurotoxin A (BoNT-A) treatment, in order to improve spasticity management in children with cerebral palsy (CP).
A total of 54 participants provided 60 plasma samples for proteomic analysis. Among them, six children were sampled before and after receiving their first BoNT-A injection. In addition, 48 unrelated children were enrolled, among whom one group had never received BoNT-A injections and another group was sampled after their first BoNT-A injection. Differentially expressed proteins were identified using the data-independent acquisition (DIA) mass spectrometry approach. Gene Ontology (GO), protein-protein interaction network, and Kyoto Encyclopedia of Genes and Genome analysis were conducted to explore the function and relationship among differentially expressed proteins. The expression levels of target proteins were verified by quantitative real-time PCR and western blotting.
Analysis identified significant differential expression of 90 proteins across two time points, including 48 upregulated and 42 downregulated proteins. The upregulated thioredoxin, α-actinin-1, and aggrecan, and the downregulated integrin beta-1 may affect the growth of muscles affected by spasticity 3 months after BoNT-A injection. This effect is potentially mediated through the activation or inhibition of PI3K-Akt, focal adhesion, and regulation of actin cytoskeleton signaling pathways.
BoNT-A injection could lead to a disruption of protein levels and signaling pathways, a condition subsequently associated with muscle growth. This finding might aid clinicians in optimizing the management of spasticity in children with CP.
本研究旨在探索与肌肉生长相关的蛋白质组学特征和特定靶蛋白，以改善脑瘫（CP）患儿痉挛的管理。
共 54 名参与者提供了 60 份血浆样本进行蛋白质组学分析。其中，6 名儿童在接受首次肉毒毒素 A（BoNT-A）注射前后接受了采样。此外，还纳入了 48 名无相关性的儿童，其中一组从未接受过 BoNT-A 注射，另一组在接受首次 BoNT-A 注射后接受了采样。使用数据非依赖性采集（DIA）质谱法鉴定差异表达蛋白。进行基因本体论（GO）、蛋白质-蛋白质相互作用网络和京都基因与基因组百科全书分析，以探讨差异表达蛋白之间的功能和关系。通过定量实时 PCR 和 Western blot 验证靶蛋白的表达水平。
分析确定了两个时间点 90 种蛋白的显著差异表达，包括 48 种上调蛋白和 42 种下调蛋白。上调的硫氧还蛋白、α-辅肌动蛋白-1 和聚集蛋白，以及下调的整合素β-1 可能会影响 BoNT-A 注射后 3 个月痉挛影响的肌肉生长。这种作用可能是通过激活或抑制 PI3K-Akt、黏着斑和肌动蛋白细胞骨架信号通路来介导的。
BoNT-A 注射可能导致蛋白质水平和信号通路的中断，从而与肌肉生长相关。这一发现可能有助于临床医生优化 CP 患儿痉挛的管理。
