The failure of the adult injured spinal cord to support axonal regeneration is in part attributed to the
glial scar. Reactive astrocytes constitute a major cellular component of the
glial scar and are heterogeneous with respect to the
extracellular matrix proteins that they secrete. Astrocytes may produce antiregenerative molecules such as
chondroitin sulphate
proteoglycans (CSPGs) or proregenerative molecules such as
laminin and
fibronectin. While many different CSPGs are expressed after
spinal cord injury (SCI) they all rely on the same
enzymes,
xylosyltransferase-I and -II (XT-I, XT-II) and
chondroitin 4-sulfotransferase (C4ST) to add the repulsive
chondroitin sulfate side chains to their core
proteins. We show that XT-I, XT-II, and C4ST are part of a CSPG biosynthetic gene (
CBG) battery. Using primary astrocyte cultures and quantitative PCR we demonstrate that TGFbeta2, PDGF, and
IL-6 induce the expression of CBGs,
laminin and
fibronectin by several-fold. We further show that over-expression of the
transcription factor SOX9 also strongly induces the expression of CBGs but does not increase the expression of
laminin or
fibronectin. Correspondingly, SOX9 knock-down in primary astrocytes causes a decrease in
CBG and an increase in
laminin and
fibronectin mRNA levels. Finally, we show that the in vivo expression profiles of TGFbeta2, PDGF,
IL-6, and SOX9 are consistent with their potential roles in differentially regulating CBGs,
laminin and
fibronectin gene expression in the injured spinal cord. This work suggests that SOX9 levels may be pivotal in determining the balance of pro- and anti-regenerative extracellular matrix molecules produced by astrocytes.