MMP proteolysis regulates the levels and the functionality of extracellular matrix components and cell surface signaling receptors. The MMP family of zinc endopeptidases (24 individual enzymes in humans) includes collagenases, gelatinases, matrilysins, stromelysins and membrane-type MMPs. Consequently, we have established that inhibition of matrix metalloproteinase (MMP) activity immediately after sciatic nerve crush facilitates nerve regrowth by enhancing the rate of SC mitosis. It has been long suspected that certain proteolytic events are involved in suppressing SC mitosis and axonal growth. As both non-myelinating and myelinating SCs de-differentiate, they up-regulate the expression of glial fibrillary acidic protein (GFAP), , required for the subsequent proliferation of SCs and the initiation of axonal regeneration. It became evident that the SC interactions with axons during the early post-injury events influence the final outcome of nerve repair. A number of molecular modulators of SC signaling have been characterized in nerve development, however, the intrinsic factors that directly contribute to the rigorous phenotypic reorganization in SCs during the nerve and myelin repair remain poorly understood. Regenerative capacity of the peripheral nervous system depends on the remarkable phenotypic plasticity of Schwann cells (SCs), ,, ,, ,, increasingly employed in the regenerative medicine approaches, ,,. The funders provided the funding to support the studies.Ĭompeting interests: The authors have declared that no competing interests exist. The work is made available under the Creative Commons CC0 public domain dedication.įunding: The funders (VA Merit Review Award (VIS), NIH/NINDS R21NS060307 (VIS), NIH/NCI R01CA83017 and R01CA157328 (AYS) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. Received: NovemAccepted: FebruPublished: March 16, 2012 PLoS ONE 7(3):Įditor: Shree Ram Singh, National Cancer Institute, United States of America (2012) The MMP-9/TIMP-1 Axis Controls the Status of Differentiation and Function of Myelin-Forming Schwann Cells in Nerve Regeneration. Pharmacological inhibition of MMP activity suppressed the expression of Na v1.7/1.8 channels in the crushed nerves.Ĭitation: Kim Y, Remacle AG, Chernov AV, Liu H, Shubayev I, Lai C, et al. These data imply that during the first days post-injury MMP-9 exhibits a functionally important anti-mitogenic activity in the wild-type mice. Our comparative studies using MMP-9 knockout and wild-type mice documented an aberrantly enhanced proliferative activity and, accordingly, an increased number of post-mitotic Schwann cells, short internodes and additional nodal abnormalities in remyelinated nerves of MMP-9 knockout mice. Knockout of the MMP-9 gene in mice resulted in elevated numbers of de-differentiated/immature mSCs in the damaged nerve. MMP-9 capture followed by gelatin zymography and Western blotting of the isolated samples revealed the presence of the MMP-9/TIMP-1 heterodimers and the activated MMP-9 enzyme in the injured nerve within the first 24 h post-injury. In the present study, using the genome-wide transcriptional profiling of normal and injured sciatic nerves in mice followed by extensive bioinformatics analyses of the data, we determined that an endogenous, specific MMP-9 inhibitor was a top up-regulated gene in the injured nerve.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |