Reactive astrocytes in glial scar attract olfactory ensheathing cells migration by secreted TNF-alpha in spinal cord lesion of rat.
BACKGROUND
After spinal cord injury (SCI), the formation of glial scar contributes to the failure of injured adult axons to regenerate past the lesion. Increasing evidence indicates that olfactory ensheathing cells (OECs) implanted into spinal cord are found to migrate into the lesion site and induce axons regeneration beyond glial scar and resumption of functions. However, little is known about the mechanisms of OECs migrating from injection site to glial scar/lesion site.


RESULTS
In the present study, we identified a link between OECs migration and reactive astrocytes in glial scar that was mediated by the tumor necrosis factor-alpha (TNF-alpha). Initially, the Boyden chamber migration assay showed that both glial scar tissue and reactive astrocyte-conditioned medium promoted OECs migration in vitro. Reactive astrocyte-derived TNF-alpha and its type 1 receptor TNFR1 expressed on OECs were identified to be responsible for the promoting effect on OECs migration. TNF-alpha-induced OECs migration was demonstrated depending on activation of the extracellular signal-regulated kinase (ERK) signaling cascades. Furthermore, TNF-alpha secreted by reactive astrocytes in glial scar was also showed to attract OECs migration in a spinal cord hemisection injury model of rat.


CONCLUSIONS
These findings showed that TNF-alpha was released by reactive astrocytes in glial scar and attracted OECs migration by interacting with TNFR1 expressed on OECs via regulation of ERK signaling. This migration-attracting effect of reactive astrocytes on OECs may suggest a mechanism for guiding OECs migration into glial scar, which is crucial for OECs-mediated axons regrowth beyond the spinal cord lesion site.
Su
Zhida
Z
Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Minister of Education, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai, China.
Yuan
Yimin
Y
Chen
Jingjing
J
Cao
Li
L
Zhu
Yanling
Y
Gao
Liang
L
Qiu
Yang
Y
He
Cheng
C
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002465:Cell Movement / Q000187:drug effects; D002921:Cicatrix / Q000473:pathology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009833:Olfactory Pathways / Q000187:drug effects / Q000201:enzymology / Q000473:pathology* / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D017077:Culture Media, Conditioned; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases