http://www.jneurosci.org/content/34/7/2438.short
-
Author contributions: C.-H.S. and C.P. designed research; C.-H.S., M.L., K.L.-B., and C.P. performed research; C.-H.S. and C.P. analyzed data; C.-H.S. and C.P. wrote the paper.
-
The Journal of Neuroscience, 12 February 2014, 34(7): 2438-2443; doi: 10.1523/JNEUROSCI.2947-13.2014
- Abstract
- Full Text
- Full Text (PDF)
Abstract
Traumatic spinal cord injury (SCI)
results in a cascade of tissue responses leading to cell death, axonal
degeneration, and
glial scar formation, exacerbating the already
hostile environment and further inhibiting axon regeneration. Overcoming
these
inhibitory cues and promoting axonal
regeneration is one of the primary targets in developing a cure for SCI.
Previously,
we demonstrated that transplantation of bone
morphogenetic protein (BMP)-induced astrocytes derived from embryonic
glial-restricted
precursors (GDAsBMP) promotes extensive axonal growth and motor function recovery in a rodent spinal cord injury model. Here, we identify periostin
(POSTN), a secreted protein, as a key component of GDABMP-induced axonal regeneration. POSTN is highly expressed by GDAsBMP and the perturbation of POSTN expression by shRNA diminished GDABMP-induced neurite extension in vitro. We also found that recombinant POSTN is sufficient to overcome the inhibitory effect of scar-associated molecules and promote
neurite extension in vitro by signaling through focal adhesion kinase and Akt. Furthermore, transplantation of POSTN-deficient GDAsBMP into the injured rat spinal cord resulted in compromised axonal regeneration, indicating that POSTN plays an essential role
in GDABMP-mediated axonal regeneration. This finding reveals not only one of the major mechanisms underlying GDABMP-dependent recovery from SCI, but also the potential of POSTN as a therapeutic agent for traumatic injury of the CNS.
No comments:
Post a Comment