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Preparation of Tunable Extracellular Matrix Microenvironments to Evaluate Schwann Cell Phenotype Specification
Published on: June 2, 2020
Sequencing analysis of matrix metalloproteinase 7-induced genetic changes in Schwann cells
Pan-Jian Lu1, Gang Wang1, Xiao-Dong Cai1
1Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province, China.
Abstract:
Previous research revealed the positive activity of matrix metalloproteinase 7 (MMP7) on migration and myelin regeneration of Schwann cells (SCs). However, understanding of the molecular changes and biological activities induced by increased amounts of MMP7 in SCs remains limited. To better understand the underlying molecular events, primary SCs were isolated from the sciatic nerve stump of newborn rats and cultured with 10 nM human MMP7 for 24 hours. The results of genetic testing were analyzed at a relatively relaxed threshold value (fold change ≥ 1.5 and P-value < 0.05). Upon MMP7 exposure, 149 genes were found to be upregulated in SCs, whereas 133 genes were downregulated. Gene Ontology analysis suggested that many differentially expressed molecules were related to cellular processes, single-organism processes, and metabolic processes. Kyoto Enrichment of Genes and Genomes pathway analysis further indicated the critical involvement of cell signaling and metabolism in MMP7-induced molecular regulation of SCs. Results of Ingenuity Pathway Analysis (IPA) also revealed that MMP7 regulates biological processes, molecular functions, cellular components, diseases and functions, biosynthesis, material metabolism, cell movement, and axon guidance. The outcomes of further analysis will deepen our comprehension of MMP7-induced biological changes in SCs. This study was approved by the Laboratory Animal Ethics Committee of Nantong University, China (approval No. 20190225-004) on February 27, 2019.
Insights
Matrix metalloproteinase 7 (MMP7) influences Schwann cell (SC) migration and myelin regeneration. This study details molecular changes in SCs following MMP7 exposure, revealing significant gene expression alterations.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Matrix metalloproteinase 7 (MMP7) is known to positively affect Schwann cell (SC) migration and myelin regeneration.
- Limited understanding exists regarding the comprehensive molecular alterations and biological activities induced by elevated MMP7 levels in SCs.
Purpose of the Study:
- To investigate the molecular events and biological activities triggered by MMP7 in primary rat Schwann cells.
- To identify genes and pathways regulated by MMP7 exposure in SCs.
Main Methods:
- Primary Schwann cells were isolated from newborn rat sciatic nerves.
- Cells were cultured with 10 nM human MMP7 for 24 hours.
- Gene expression analysis (including Gene Ontology and Kyoto Enrichment of Genes and Genomes pathway analysis) was performed using a relaxed threshold (fold change ≥ 1.5, P-value < 0.05).
Main Results:
- MMP7 exposure led to significant differential gene expression: 149 genes upregulated and 133 genes downregulated.
- Gene Ontology analysis indicated involvement in cellular, single-organism, and metabolic processes.
- Pathway analysis highlighted MMP7's role in cell signaling, metabolism, cell movement, and axon guidance.
Conclusions:
- MMP7 significantly alters gene expression in Schwann cells, impacting key biological processes.
- These findings provide deeper insights into the molecular mechanisms underlying MMP7's effects on SCs, relevant to myelin regeneration and nerve repair.
