Oligodendrocyte Precursor Cells Support Blood-Brain Barrier Integrity via TGF-β Signaling
Seo, Ji Hae
Liang, Anna C.
Pham, Loc-Duyen D.
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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.
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