title: Trafficking and secretion of matrix metalloproteinase-2 in olfactory ensheathing glial cells: A role in cell migration?
abstract: Olfactory ensheathing cells (OECs) are unique glia found only in the olfactory system. They retain exceptional plasticity and support olfactory neurogenesis and retargeting across the PNS:CNS boundary in the olfactory system. OECs have been shown to improve functional outcome when transplanted into rodents with spinal cord injury. The growth-promoting properties of implanted OECs encompass their ability to migrate through the scar tissue and render it more permissive for axonal outgrowth, but the underlying molecular mechanisms remain poorly understood. OECs appear to regulate molecules of the extracellular matrix (ECM) that inhibit axonal growth. Among the proteins that have the potential to promote cell migration, axonal regeneration and remodeling of the ECM are matrix metalloproteinases (MMPs), a family of endopeptidases that cleave matrix, soluble, and membrane-bound proteins and that are regulated by their endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs). Little is known about MMP/TIMP trafficking, secretion, and role in OECs. Using a combination of cell biology, biochemistry, pharmacology, and imaging techniques, we show that MMP-2 and MMP-9 are expressed and proteolytically active in the olfactory epithelium and in particular in the OECs of the lamina propria. These proteinases and regulatory proteins such as MT1-MMP and TIMP-2 are expressed in cultured OECs. MMPs exhibit nuclear localization and vesicular trafficking and secretion, with distribution along microtubules and microfilaments and co-localization with the molecular motor protein kinesin. Finally, we show that MMPs are involved in migration of OECs in vitro on different ECM substrates.
authors.affiliation: Neurobiologie des Interactions Cellulaires et Neurophysiopathologie, UMR 6184 CNRS-Université Aix-Marseille II, Faculté de Médecine, CS80011, Bd Pierre Dramard, 13344 Marseille Cedex 15, France.
authors.forename: Yatma
authors.initials: Y
authors.lastname: Gueye
authors.forename: Lotfi
authors.initials: L
authors.lastname: Ferhat
authors.forename: Oualid
authors.initials: O
authors.lastname: Sbai
authors.forename: John
authors.initials: J
authors.lastname: Bianco
authors.forename: Adlane
authors.initials: A
authors.lastname: Ould-Yahoui
authors.forename: Anne
authors.initials: A
authors.lastname: Bernard
authors.forename: Eliane
authors.initials: E
authors.lastname: Charrat
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Chauvin
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Risso
authors.forename: François
authors.initials: F
authors.lastname: Féron
authors.forename: Santiago
authors.initials: S
authors.lastname: Rivera
authors.forename: Michel
authors.initials: M
authors.lastname: Khrestchatisky
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D005260:Female; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000166:cytology / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
chemical_list: D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9