Other
14 Authors
- Maeda M,
- Pham LD,
- Arai K,
- Suwa F,
- Taguchi A,
- Ihara M,
- Lo EH,
- Hayakawa K,
- Matsuyama T,
- Kim KW,
- Maki T,
- Liang AC,
- Seo JH,
- Miyamoto N
| First Author | Seo JH | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 7 | Pages | e103174 |
| PubMed ID | 25078775 | Mgi Jnum | J:218997 |
| Mgi Id | MGI:5619233 | Doi | 10.1371/journal.pone.0103174 |
| Citation | Seo JH, et al. (2014) Oligodendrocyte precursor cells support blood-brain barrier integrity via TGF-beta signaling. PLoS One 9(7):e103174 |
| abstractText | Trophic 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-beta1 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-beta-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-beta1 is knocked down specifically in OPCs. Neonates of these OPC-specific TGF-beta1 deficient mice (OPC-specific TGF-beta1 partial KO mice: PdgfraCre/Tgfb1flox/wt mice or OPC-specific TGF-beta1 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-beta 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. |
