Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=26384335
&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215
Effects of Reducing Suppressors of Cytokine Signaling-3 (SOCS3) Expression on
Dendritic Outgrowth and Demyelination after Spinal Cord Injury
#MMPMID26384335
Park KW
; Lin CY
; Li K
; Lee YS
PLoS One
2015[]; 10
(9
): e0138301
PMID26384335
show ga
Suppressors of cytokine signaling-3 (SOCS3) is associated with limitations of
nerve growth capacity after injury to the central nervous system. Although
genetic manipulations of SOCS3 can enhance axonal regeneration after optic
injury, the role of SOCS3 in dendritic outgrowth after spinal cord injury (SCI)
is still unclear. The present study investigated the endogenous expression of
SOCS3 and its role in regulating neurite outgrowth in vitro. Interleukin-6 (IL-6)
induces SOCS3 expression at the mRNA and protein levels in neuroscreen-1 (NS-1)
cells. In parallel to SOCS3 expression, IL-6 induced tyrosine phosphorylation of
signal transducer and activator of transcription 3 (STAT3) in NS-1 cells.
Lentiviral delivery of short hairpin RNA (shSOCS3) (Lenti-shSOCS3) to decrease
SOCS3 expression into NS-1 cells enhanced IL-6-induced tyrosine phosphorylation
of STAT3 (P-STAT3 Tyr705) and promoted neurite outgrowth. In addition, we
determined if reduction of SOCS3 expression by microinjection of Lenti-shSOCS3
into spinal cord enhances dendrite outgrowth in spinal cord neurons after SCI.
Knocking down of SOCS3 in spinal cord neurons with Lenti-shSOCS3 increased
complete SCI-induced P-STAT3 Tyr705. Immunohistochemical analysis showed that
complete SCI induced a significant reduction of microtubule association protein
2-positive (MAP-2+) dendrites in the gray and white matter at 1 and 4 weeks after
injury. The SCI-induced reduction of MAP-2+ dendrites was inhibited by infection
with Lenti-shSOCS3 in areas both rostral and caudal to the lesion at 1 and 4
weeks after complete SCI. Furthermore, shSOCS3 treatment enhanced up-regulation
of growth associated protein-43 (GAP-43) expression, which co-localized with
MAP-2+ dendrites in white matter and with MAP-2+ cell bodies in gray matter,
indicating Lenti-shSOCS3 may induce dendritic regeneration after SCI. Moreover,
we demonstrated that Lenti-shSOCS3 decreased SCI-induced demyelination in white
matter of spinal cord both rostral and caudal to the injury site 1 week
post-injury, but not rostral to the injury at 4 weeks post-injury. Importantly,
similar effects as Lenti-shSOCS3 on increasing MAP-2+ intensity and dendrite
length, and preventing demyelination were observed when a second shSOCS3
(Lenti-shSOCS3 #2) was applied to rule out the possibilities of off target
effects of shRNA. Collectively, these results suggest that knocking down of SOCS3
enhances dendritic regeneration and prevents demyelination after SCI.
free
free
free
