Matrix metalloproteinase‐2 is involved in myelination of dorsal root ganglia neurons

Abstract

Matrix metalloproteinases (MMPs) comprise a large family of endopeptidases that are capable of degrading all extracellular matrix components. There is increasing evidence that MMPs are not only involved in tissue destruction but may also exert beneficial effects during axonal regeneration and nerve remyelination. Here, we provide evidence that MMP-2 (gelatinase A) is associated with the physiological process of myelination in the peripheral nervous system (PNS). In a myelinating co-culture model of Schwann cells and dorsal root ganglia neurons, MMP-2 expression correlated with the degree of myelination as determined by immunocytochemistry, zymography, and immunosorbent assay. Modulation of MMP-2 activity by chemical inhibitors led to incomplete and aberrant myelin formation. In vivo MMP-2 expression was detected in the cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome as well as in CSF and sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy. Our findings suggest an important, previously unrecognized role for MMP-2 during myelination in the PNS. Endogenous or exogenous modulation of MMP-2 activity may be a relevant target to enhance regeneration in demyelinating diseases of the PNS.

Correlation of matrix metalloproteinases‐2 and ‐9 with proinflammatory cytokines in Guillain‐Barré syndrome

“…MMP-9 was also found to be localized around the blood vessels in human nerve biopsies from GBS patients, indicating its potential role in the disease (Kieseier et al, 1998). In the CSF of GBS patients, MMP-2 levels were significantly up-regulated and correlated with disease duration (Lehmann et al, 2009). Our results are in accordance with earlier reports showing up-regulation of MMP-2 and MMP-9 by proinflammatory cytokines during disease progression (Abraham et al, 2005) and down-regulation of MMP-9 in the recovery phase of the disease (Creange et al, 1999).…”

Human Schwann Cells Retain Essential Phenotype Characteristics After Immortalization

“…Myelinating cultures. Myelinating cultures were prepared as described previously [21,22]. Embryonic dorsal root ganglia (DRG) were prepared from E15 rat pups.…”

Schwann cells reposition a peripheral nerve to isolate it from postembryonic remodeling of its targets

“…5E,F). Because Schwann cells can express matrix metalloproteases (MMPs) (Ferguson and Muir, 2000;La Fleur et al, 1996;Lehmann et al, 2009;Mantuano et al, 2008), which cleave extracellular matrix components (Page-McCaw et al, 2007), and can secrete a basement membrane that surrounds 3647 RESEARCH ARTICLE Schwann cells reposition nerves mature nerves (Prockop and Kivirikko, 1995), the simplest possibility is that Schwann cells directly secrete a new basement membrane superficial to the PLLn while degrading the deep basement membrane.…”

“…Additionally, Schwann cells activate MMP expression following nerve injury, and MMPs have been implicated in Schwann cell myelination (Ferguson and Muir, 2000;La Fleur et al, 1996;Lehmann et al, 2009;Mantuano et al, 2008). Intriguingly, MMP2 was recently shown to have a role in degrading the basement membrane to allow dendrite remodeling in Drosophila sensory neurons (Yasunaga et al, 2010).…”