Oligodendrocyte Precursor Cells Support Blood-Brain Barrier Integrity via TGF-β Signaling
Seo, Ji Hae
Liang, Anna C.
Pham, Loc-Duyen D.
MetadataShow full item record
CitationSeo, J. H., T. Maki, M. Maeda, N. Miyamoto, A. C. Liang, K. Hayakawa, L. D. Pham, et al. 2014. “Oligodendrocyte Precursor Cells Support Blood-Brain Barrier Integrity via TGF-β Signaling.” PLoS ONE 9 (7): e103174. doi:10.1371/journal.pone.0103174. http://dx.doi.org/10.1371/journal.pone.0103174.
AbstractTrophic coupling between cerebral endothelium and their neighboring cells is required for the development and maintenance of blood-brain barrier (BBB) function. Here we report that oligodendrocyte precursor cells (OPCs) secrete soluble factor TGF-β1 to support BBB integrity. Firstly, we prepared conditioned media from OPC cultures and added them to cerebral endothelial cultures. Our pharmacological experiments showed that OPC-conditioned media increased expressions of tight-junction proteins and decreased in vitro BBB permeability by activating TGB-β-receptor-MEK/ERK signaling pathway. Secondly, our immuno-electron microscopic observation revealed that in neonatal mouse brains, OPCs attach to cerebral endothelial cells via basal lamina. And finally, we developed a novel transgenic mouse line that TGF-β1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-β1 deficient mice (OPC-specific TGF-β1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-β1 total KO mice: PdgfraCre/Tgfb1flox/flox mice) exhibited cerebral hemorrhage and loss of BBB function. Taken together, our current study demonstrates that OPCs increase BBB tightness by upregulating tight junction proteins via TGF-β signaling. Although astrocytes and pericytes are well-known regulators of BBB maturation and maintenance, these findings indicate that OPCs also play a pivotal role in promoting BBB integrity.
Citable link to this pagehttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12785957
- HMS Scholarly Articles 
Contact administrator regarding this item (to report mistakes or request changes)