The glycoprotein fibulin-3 regulates morphology and motility of olfactory ensheathing cells in vitro.
The primary olfactory pathway in adult mammals has retained a remarkable potential for self-repair. A specialized glial cell within the olfactory nerve, called olfactory ensheathing cell (OEC), and their associated extracellular matrix are thought to play an important role during regenerative events in this system. To gain insight into novel molecules that could mediate the OEC-supported growth of axons within the olfactory nerve, gene expression profiling experiments were conducted which revealed high expression of the glycoprotein fibulin-3 in OECs. This observation was confirmed with quantitative PCR. In vivo, the distribution of all members of the fibulin family, fibulin-3 included, was localized to the lamina propria underneath the olfactory epithelium, in close association within olfactory nerve bundles. To manipulate fibulin-3 gene expression in cultured OECs, lentiviral vector constructs were designed to either transgenically express or knock-down fibulin-3. Experimental data showed that increased levels of fibulin-3 induced profound morphological changes in cultured OECs, impeded with their migratory abilities and also suppressed OEC-mediated neurite outgrowth. Knock-down of fibulin-3 levels resulted in reduced OEC proliferation. In conclusion, the data provide novel insights into a putative role for fibulin-3 in the regulation of cell migration and neurite outgrowth within the primary olfactory pathway.
Vukovic
Jana
J
School of Anatomy and Human Biology, The University of Western Australia, Crawley, Western Australia, Australia. jvukovic@anhb.uwa.edu.au
Ruitenberg
Marc J
MJ
Roet
Kasper
K
Franssen
Elske
E
Arulpragasam
Ajanthy
A
Sasaki
Takako
T
Verhaagen
Joost
J
Harvey
Alan R
AR
Busfield
Samantha J
SJ
Plant
Giles W
GW
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D016000:Cluster Analysis; D018920:Coculture Techniques / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling / Q000379:methods; D018014:Gene Transfer Techniques; D016501:Neurites / Q000502:physiology; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D009830:Olfactory Bulb / Q000166:cytology*; D009833:Olfactory Pathways / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012583:Schwann Cells / Q000502:physiology; D018709:Statistics, Nonparametric; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism
D002135:Calcium-Binding Proteins; D034741:RNA, Small Interfering; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; C060820:fibulin; D001973:Bromodeoxyuridine