Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-β production

被引：258

作者：

Dohgu, S

Takata, F

Yamauchi, A

Nakagawa, S

Egawa, T

Naito, M

Tsuruo, T

Sawada, Y

Niwa, M

Kataoka, Y

机构：

[1] Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Jonan Ku, Fukuoka 8140180, Japan

[2] Nagasaki Univ, Grad Sch Med, Dept Pharmacol 1, Nagasaki 8528523, Japan

[3] Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan

[4] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Med Pharmaceut Sci, Higashi Ku, Fukuoka 8128582, Japan

来源：

BRAIN RESEARCH | 2005年 / 1038卷 / 02期

基金：

日本学术振兴会;

关键词：

blood-brain barrier; pericyte; transforming growth factor-beta; P-glycoprotein; permeability; mouse brain endothelial cell;

D O I：

10.1016/j.brainres.2005.01.027

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The blood-brain barrier (BBB) is a highly organized multicellular complex consisting of an endothelium, brain pericytes and astrocytes. The present study was aimed at evaluating the role of brain pericytes in the induction and maintenance of BBB functions and involvement of transforming growth factor-beta (TGF-beta) in the functional properties of pericytes. We used an in vitro BBB model established by coculturing immortalized mouse brain capillary endothelial (MBEC4) cells with a primary culture of rat brain pericytes. The coculture with rat pericytes significantly decreased the permeability to sodium fluorescein and the accumulation of rhodamine 123 in MBEC4 cells, suggesting that brain pericytes induce and up-regulate the BBB functions. Rat brain pericytes expressed TGF-beta 1 mRNA. The pericyte-induced enhancement of BBB functions was significantly inhibited when cells were treated with anti-TGF-beta l antibody (10 mu g/ml) or a TGF-beta type I receptor antagonist (SB431542) (10 mu M) for 12 h. In MBEC4 monolayers, a 12 h exposure to TGF-beta 1 (1 ng/ml) significantly facilitated the BBB functions, this facilitation being blocked by SB431542. These findings suggest that brain pericytes contribute to the up-regulation of BBB functions through continuous TGF-beta production. (c) 2005 Elsevier B.V. All rights reserved.

引用

页码：208 / 215

页数：8

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