Genes Associated with Adult Axon Regeneration Promoted by Olfactory Ensheathing Cells: A New Role for Matrix Metalloproteinase 2

Abstract

The molecular mechanisms used by olfactory ensheathing cells (OECs) to promote repair in the damaged adult mammalian CNS remain unknown. Thus, we used microarrays to analyze three OEC populations with different capacities to promote axonal regeneration in cultured rat retinal neurons. Gene expression in "long-term cultured OECs" that do not stimulate adult axonal outgrowth was compared with that of "primary olfactory ensheathing cells" and the immortalized OEC cell line TEG3. In this way, we identified a number of candidate genes that might play a role in promoting adult axonal regeneration. Among these genes, it was striking that both the matrix metalloproteinase 2 (MMP2) and an inhibitor of this protease were represented. The disruption of MMP2 activity in TEG3 cells impaired their capacity to trigger axon regeneration in cultured adult retinal neurons. Furthermore, the MMP2 protein was detected in grafts of OECs that elicited robust axonal regeneration in the injured spinal cord of adult rats in vivo. These data suggest that MMP2 does indeed participate in adult axonal regeneration induced by OECs.

Myelin-associated proteins block the migration of olfactory ensheathing cells: an in vitro study using single-cell tracking and traction force microscopy

“…In addition, this cell line shows all the types of morphology described for primary OECs in culture (Moreno-Flores et al, 2006;. In a first set of experiments, we characterized the TEG3 cell line in our culture conditions (Fig.…”

“…Given their axon growth-promoting properties, natural or genetically modified OECs have been studied extensively and transplanted into the injured spinal cord to promote axonal regeneration (Ramon-Cueto and Nieto- Sampedro, 1994;Li et al, 1997;Ramon-Cueto et al, 1998;Navarro et al, 1999;Ramon-Cueto et al, 2000;Ruitenberg et al, 2002;Garcia-Alias et al, 2004;MorenoFlores et al, 2006). Thus, OEC transplantation has emerged as a promising therapy for spinal cord injuries and for other neural diseases (Moreno-Flores and Avila, 2006;Raisman, 2007;Ramon-Cueto and Munoz-Quiles, 2010). Several OEC subpopulations have been identified in the olfactory system on the basis of their topographical distribution, distinctive morphology, intracellular cytoskeletal distribution and antigenic or gene expression profiles (Au and Roskams, 2003;Vincent et al, 2005;Guerout et al, 2010;Windus et al, 2010).…”

Neurotrophin receptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome

“…Immunohistochemistry was performed with antibodies that identified immunoreactivity for Neu-N, a nuclear protein found in the nuclei of mature neurons (1:1000 dilution; Chemicon-Millipore, Billerica, MA, USA), and for the NT receptors: p75 NTR , TrkB, TrkA and TrkC (all diluted 1:30; Santa Cruz Biotechnology, Santa Cruz, CA, USA). According to the manufacturers and as already verified in selected references [18,[44][45][46][47][48], these antibodies recognize a single band in western blot and show no cross-reactivity with other NT receptors. Briefly, paraffin embedded MTLE and control hippocampi were processed together for each antibody as described in Kandratavicius et al [7], with overnight incubation at room temperature and developed simultaneously for 10 min in 0.05% 3,3'-diaminobenzidine tetrahydrochloride (Pierce, Rockford, USA) and 0.01% hydrogen peroxide (Merck, Darmstadt, Germany).…”

Ginsenoside Rg1 Promotes the Migration of Olfactory Ensheathing Cells <i>via</i> the PI3K/Akt Pathway to Repair Rat Spinal Cord Injury

“…Furthermore, the downregulation of MMP-2 and MMP-9 also suppresses cell migration. [25][26][27] NCAM1, which is a major component of OEC-induced corticospinal axon elongation, plays a key role in OEC migration. 28,29) The RT-PCR findings indicate that ginsenoside Rg1 increased the expression of MMP-2, MMP-9, and NCAM1 genes, which stimulate ginsenoside Rg1 in enhancing the migration characteristic of OECs.…”