Matrix metalloproteinase-2 is involved in myelination of dorsal root ganglia neurons.
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.
Lehmann
Helmar C
HC
Department of Neurology, Heinrich-Heine-University, Moorenstrasse, Düsseldorf, Germany. helmar.lehmann@uni-duesseldorf.de
Köhne
Angelika
A
Bernal
Fabian
F
Jangouk
Parastoo
P
Meyer Zu Hörste
Gerd
G
Dehmel
Thomas
T
Hartung
Hans-Peter
HP
Previtali
Stefano C
SC
Kieseier
Bernd C
BC
D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005727:Ganglia, Spinal / Q000473:pathology / Q000502:physiology*; D015870:Gene Expression; D020275:Guillain-Barre Syndrome / Q000503:physiopathology; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000134:cerebrospinal fluid / Q000378:metabolism*; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000502:physiology*; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology*; D016133:Polymerase Chain Reaction; D020277:Polyradiculoneuropathy, Chronic Inflammatory Demyelinating / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D013497:Sural Nerve / Q000473:pathology / Q000503:physiopathology
D016207:Cytokines; D012333:RNA, Messenger; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat