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Neural Regen Res. 2020 Mar;15(3):503-511. doi: 10.4103/1673-5374.266062.

Protein microarray analysis of cytokine expression changes in distal stumps after sciatic nerve transection.

Author information

1
Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Institute of Orthopedics, Chinese PLA General Hospital, Beijing, China.
2
Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Institute of Orthopedics, Chinese PLA General Hospital, Beijing; The First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China.
3
Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province; Department of Neurosurgery, Chinese PLA General Hospital, Beijing, China.
4
Beijing Key Laboratory of Regenerative Medicine in Orthopedics, Institute of Orthopedics, Chinese PLA General Hospital, Beijing; Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.

Abstract

A large number of chemokines, cytokines, other trophic factors and the extracellular matrix molecules form a favorable microenvironment for peripheral nerve regeneration. This microenvironment is one of the major factors for regenerative success. Therefore, it is important to investigate the key molecules and regulators affecting nerve regeneration after peripheral nerve injury. However, the identities of specific cytokines at various time points after sciatic nerve injury have not been determined. The study was performed by transecting the sciatic nerve to establish a model of peripheral nerve injury and to analyze, by protein microarray, the expression of different cytokines in the distal nerve after injury. Results showed a large number of cytokines were up-regulated at different time points post injury and several cytokines, e.g., ciliary neurotrophic factor, were downregulated. The construction of a protein-protein interaction network was used to screen how the proteins interacted with differentially expressed cytokines. Kyoto Encyclopedia of Genes and Genomes pathway and Gene ontology analyses indicated that the differentially expressed cytokines were significantly associated with chemokine signaling pathways, Janus kinase/signal transducers and activators of transcription, phosphoinositide 3-kinase/protein kinase B, and notch signaling pathway. The cytokines involved in inflammation, immune response and cell chemotaxis were up-regulated initially and the cytokines involved in neuronal apoptotic processes, cell-cell adhesion, and cell proliferation were up-regulated at 28 days after injury. Western blot analysis showed that the expression and changes of hepatocyte growth factor, glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were consistent with the results of protein microarray analysis. The results provide a comprehensive understanding of changes in cytokine expression and changes in these cytokines and classical signaling pathways and biological functions during Wallerian degeneration, as well as a basis for potential treatments of peripheral nerve injury. The study was approved by the Institutional Animal Care and Use Committee of the Chinese PLA General Hospital, China (approval number: 2016-x9-07) in September 2016.

KEYWORDS:

Kyoto Encyclopedia of Genes and Genomes pathway; Wallerian degeneration; cytokines; distal stump; gene ontology; peripheral nerve injury; protein microarray; protein-protein interaction network

PMID:
31571662
DOI:
10.4103/1673-5374.266062
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