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A Rapid, Scalable Method for the Isolation, Functional Study, and Analysis of Cell-derived Extracellular Matrix
Published on: January 4, 2017
Extracellular matrix and matrix metalloproteinases in sciatic nerve
C I Platt1, C A Krekoski, R V Ward
1School of Biological Sciences, University of East Anglia, Norwich, United Kingdom.
Abstract:
Although matrix metalloproteinases (MMPs) are increasingly being implicated in several pathologies of the nervous system, it is not yet clear what role they play in normal neurobiological processes. We review the expression of extracellular matrix (ECM) components as well as MMPs and tissue inhibitors of metalloproteinases (TIMPs) in the peripheral nervous system. We explore the expression of certain MMPs and the four TIMPs at the mRNA level in the postnatal mouse sciatic nerve. In addition, we have used substrate gel and in situ zymography to determine levels of MMP-2 and -9 and TIMP activity in rat sciatic nerve after crush and during regeneration. A rapid and transient increase in MMP-9 localised at and immediately distal to the site of injury was observed, whereas an increase in MMP-2 activity was delayed, prolonged, and extended proximal and distal to the injury site. This activity coincides with periods of axonal elongation, suggesting that it could act to facilitate axonal extension along the nerve matrix. We also detected multiple species of gelatinolytic inhibitory activity, including TIMP-1 and -3 in control and injured nerve. These activities probably act to prevent uncontrolled gelatinolytic activity, maintaining nerve integrity at the level essential for axonal regrowth.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play crucial roles in peripheral nerve regeneration. MMP-9 and MMP-2 activity changes correlate with axonal regrowth after injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are implicated in nervous system pathologies.
- The role of MMPs in normal neurobiology, particularly the peripheral nervous system (PNS), is not fully understood.
- Extracellular matrix (ECM) components, MMPs, and tissue inhibitors of metalloproteinases (TIMPs) are key players in nerve function.
Purpose of the Study:
- To investigate the expression and activity of MMPs and TIMPs in the peripheral nervous system.
- To explore the role of MMPs and TIMPs in nerve injury and regeneration.
- To understand how these enzymes influence axonal extension and nerve integrity.
Main Methods:
- Review of existing literature on ECM, MMPs, and TIMPs in the PNS.
- Analysis of MMP and TIMP mRNA expression in postnatal mouse sciatic nerve.
- Substrate gel and in situ zymography to assess MMP-2, MMP-9, and TIMP activity in rat sciatic nerve after crush injury and during regeneration.
Main Results:
- MMP-9 activity rapidly and transiently increased at the injury site.
- MMP-2 activity showed a delayed, prolonged increase extending both proximally and distally.
- TIMP-1 and TIMP-3 activities were detected in both control and injured nerves, regulating gelatinolytic activity.
Conclusions:
- Dynamic changes in MMP-2 and MMP-9 activity are associated with peripheral nerve regeneration.
- MMP-2 activity may facilitate axonal extension by modifying the nerve matrix.
- TIMPs are crucial for maintaining nerve integrity by controlling MMP activity during regrowth.
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