Sohn J, Selvaraj V, Wakayama K, Orosco L, Lee E, Crawford SE, Guo F, Lang J, Horiuchi M, Zarbalis K, Itoh T, Deng W, Pleasure D. PEDF Is a Novel Oligodendrogenic Morphogen Acting on the Adult SVZ and Corpus Callosum. J Neurosci. 2012; 32:12152-64
Pigment epithelium-derived factor
(PEDF) is a serine protease inhibitor (serpin) protein with well
established neuroprotective and anti-angiogenic properties. Recent
studies have also shown that PEDF enhances renewal of adult
subventricular zone (SVZ) neural precursors. In neurosphere cultures
prepared from the SVZ of adult mice, we found that addition of
recombinant PEDF to the medium enhanced expressions of oligodendroglial
lineage markers (NG2 and PDGFrα) and transcription factors (Olig1,
Olig2, and Sox10). Similarly, continuous PEDF administration into the
lateral ventricles of adult glial fibrillary acidic protein:green
fluorescent protein (GFAP:GFP) transgenic mice increased the proportions
of GFAP:GFP+ and GFAP:GFP- SVZ neural precursors coexpressing
oligodendroglial lineage markers and transcription factors. Notably,
PEDF infusion also resulted in an induction of doublecortin- and Sox10
double-positive cells in the adult SVZ. Immunoreactive PEDF receptor was
detectable in multiple cell types in both adult SVZ and corpus
callosum. Furthermore, PEDF intracerebral infusion enhanced survival and
maturation of newly born oligodendroglial progenitor cells in the
normal corpus callosum, and accelerated oligodendroglial regeneration in
lysolecithin-induced corpus callosum demyelinative lesions. Western
blot analysis showed a robust upregulation of endogenous PEDF in the
corpus callosum upon lysolecithin-induced demyelination. Our results
document previously unrecognized oligodendrotrophic effects of
recombinant PEDF on the adult SVZ and corpus callosum, demonstrate
induction of endogenous CNS PEDF production following demyelination, and
make PEDF a strong candidate for pharmacological intervention in
demyelinative diseases.
Pigment epithelium-derived factor (PEDF) also known as serpin F1 (SERPINF1), is a multifunctional secreted protein that has anti-angiogenic, anti-tumorigenic, and neurotrophic functions. This protein may protect nerves from damage in some studies and this study suggests that it can promote survival and helps the maturation of immature oligodendrocytes. This suggests that it is a new part of the potential armoury that is going to part of the process to drive myelin repair. This will be via production and maturation of oligodendrocyte precursors to produce myelinating oligodendrocytes and so facilitate remyelination. However, on a negative side it has been shown to stimulate the development of type II diabetes when produced by fat cells which may limits its use as a drug target
Labels: remyelination