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| Status |
Public on Feb 28, 2012 |
| Title |
Matrix metalloproteinase-9 and TIMP-1 in peripheral nerve: Implications for myelin formation |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
|
| Summary |
Remyelination is a key step in functional nerve regeneration performed by Schwann cells (SC). We have demonstrated that matrix metalloproteinase (MMP)-9 is a major regulator of signal transduction and phenotypic switching in SCs. Herein, genome-wide transcriptional profiling, followed by Ingenuity Pathway Analysis revealed the MMP-9 signaling network and its endogenous inhibitor, TIMP-1, among the top induced genes of the injured sciatic nerve, that co-distributed with MMP-9 in myelinating SCs and the paranodal/nodal areas of myelinated fibers. Homo- and heterodimers of the active and proMMP-9 were purified from injured nerves using gelatin-sepharose. MMP-9 gene deletion increased the number of immature, GFAP+ mSC and post-mitotic cell counts that correlate with shorter myelin internodes in remyelinated fibers lacking MMP-9. MMP-9 is essential to nodal clustering of voltage-gated Na+ (Nav) channels. MMP inhibitor therapy diminished the expression of Nav 1.7 and 1.8. These data established the essential role of MMP-9 in guiding SC differentiation toward myelin production and in molecular assembly of the myelin domains. Modification of Nav channels in myelinated fibers may thus provide an important therapeutic approach for a number of facilitates regeneration and attenuated neuropathic pain.
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| Overall design |
Gene expression profiling of total RNAs extracted from murine sciatic nerves, dorsal root ganglion and spinal cords at day 1 and day 5 post injury.
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| Contributor(s) |
Chernov AV, Shubayev V, Strongin AY |
| Citation(s) |
22438979 |
| Submission date |
Nov 03, 2011 |
| Last update date |
Jun 14, 2018 |
| Contact name |
Andrei Chernov |
| E-mail(s) |
achernov@ucsd.edu
|
| Phone |
858 952 2854
|
| Organization name |
University of California San Diego
|
| Department |
Anesthesiology
|
| Lab |
Chernov Lab
|
| Street address |
9500 Gilman Dr
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL6885 |
Illumina MouseRef-8 v2.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA148677 |
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