Papers by Veronica Shubayev
Journal of Biological Chemistry, 2014
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PLoS ONE, 2012
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Glia, 2009
Phenotypic remodeling of Schwann cells is required to ensure successful regeneration of damaged p... more Phenotypic remodeling of Schwann cells is required to ensure successful regeneration of damaged peripheral axons. After nerve damage, Schwann cells produce an over 100-fold increase in metalloproteinase-9 (MMP-9), and therapy with an MMP inhibitor increases the number of resident (but not infiltrating) cells in injured nerve. Here, we demonstrate that MMP-9 regulates proliferation and trophic signaling of Schwann cells. Using in vivo BrdU incorporation studies of axotomized sciatic nerves of MMP-9-/- mice, we found increased Schwann cell mitosis in regenerating (proximal) stump relative to wild-type mice. Treatment of cultured primary Schwann cells with recombinant MMP-9 suppressed their growth, mitogenic activity, and produced a dose-dependent, biphasic, and selective activation of ERK1/2, but not JNK and p38 MAPK. MMP-9 induced ERK1/2 signaling in both undifferentiated and differentiated (using dbcAMP) Schwann cells. Using inhibitors to MEK and trophic tyrosine kinase receptors, we established that MMP-9 regulates Ras/Raf/MEK-ERK pathways through IGF-1, ErbB, and PDGF receptors. We also report on the early changes of MMP-9 mRNA expression (within 24 h) after axotomy. These studies establish that MMP-9 controls critical trophic signal transduction pathways and phenotypic remodeling of Schwann cells.
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Frontiers in Neuroscience, 2009
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The Journal of biological chemistry, Jan 19, 2015
To shed light on the early immune response processes in severed peripheral nerve, we performed ge... more To shed light on the early immune response processes in severed peripheral nerve, we performed genome-wide transcriptional profiling and bioinformatics analyses of the proximal (P; regenerating) and distal (D; degenerating) nerve stumps at day 1 in the sciatic nerve axotomy model in rats. Multiple cell death-related pathways were activated in the degenerating D stump, whereas activation of the cytoskeletal motility and gluconeogenesis/glycolysis pathways was most prominent in the P stump of the axotomized nerve. Our bioinformatics analyses also identified the specific immunomodulatory genes of the chemokine, interleukin (IL), tumor necrosis factor (TNF), major histocompatibility complex (MHC), immunoglobulin-binding Fc receptor, calcium-binding S100, matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP), and ion channel families affected in both the P and D segments. S100a8 and S100a9 were the top up-regulated genes in both the P and D segments. Stimulation of...
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Pain, 2014
PI3-kinases (PI3Ks) participate in nociception within spinal cord, dorsal root ganglion (DRG), an... more PI3-kinases (PI3Ks) participate in nociception within spinal cord, dorsal root ganglion (DRG), and peripheral nerves. To extend our knowledge, we immunohistochemically stained for each of the 4 class I PI3K isoforms along with several cell-specific markers within the lumbar spinal cord, DRG, and sciatic nerve of naive rats. Intrathecal and intraplantar isoform specific antagonists were given as pretreatments before intraplantar carrageenan; pain behavior was then assessed over time. The α-isoform was localized to central terminals of primary afferent fibers in spinal cord laminae IIi to IV as well as to neurons in ventral horn and DRG. The PI3Kβ isoform was the only class I isoform seen in dorsal horn neurons; it was also observed in DRG, Schwann cells, and axonal paranodes. The δ-isoform was found in spinal cord white matter oligodendrocytes and radial astrocytes, and the γ-isoform was seen in a subpopulation of IB4-positive DRG neurons. No isoform co-localized with microglial mark...
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Molecular and Cellular Neuroscience, 2006
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The International journal of oral & maxillofacial implants
To test in a rat model whether quantitative percussion diagnostics provide reliable, reproducible... more To test in a rat model whether quantitative percussion diagnostics provide reliable, reproducible indications of osseointegration. Titanium implants were placed in femurs of 36 Sprague-Dawley rats. Each animal was assigned to one of six groups defined by one of three time points (2, 4, or 8 weeks postplacement) and one of two treatments (matrix metalloproteinase [MMP] inhibitor GM6001 or control). Percussion testing was conducted three times per subject at implant placement and before sacrifice at one of the time points. For each time point, there was an experimental group that received daily intraperitoneal injections of GM6001, and a control group that received no MMP inhibitor. The percussion data consisted of loss coefficient (LC) values that characterize energy dissipation. Statistical analysis was performed on the LC values for the two animal groups using the paired Student t test to assess differences as a function of time, and the independent t test to compare mean LC for th...
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Spine, 2000
Wolters Kluwer Health may email you for journal alerts and information, but is committed to maint... more Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. ... Skip Navigation Links Home > ...
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Journal of Neuroimmunology, 2001
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European Journal of Neuroscience, 2006
Campana, WM, Li, X., Shubayev, VI, Angert, M., Cai, K. and Myers, RR (2006), Erythropoietin reduc... more Campana, WM, Li, X., Shubayev, VI, Angert, M., Cai, K. and Myers, RR (2006), Erythropoietin reduces Schwann cell TNF-α, Wallerian degeneration and pain-related behaviors after peripheral nerve injury. European Journal of Neuroscience, 23: 617626. doi: 10.1111/j. ...
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Brain, Behavior, and Immunity, 2007
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Brain Research, 2000
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Journal of Biological Chemistry, 2014
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Papers by Veronica Shubayev