Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-β production
Brain pericytes contribute to the induction and up-regulation of blood-brain barrier functions through transforming growth factor-β production
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DOI：
10.1016/j.brainres.2005.01.027
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发表时间：
2005-03-21
期刊：
影响因子：
2.9
通讯作者：
Kataoka, Y
中科院分区：
文献类型：
--
作者：
Dohgu, S;Takata, F;Kataoka, Y
血脑屏障(BBB)是一种高度组织化的多细胞复合体，由内皮细胞、脑周细胞和星形胶质细胞组成。本研究旨在评价脑周细胞在血脑屏障功能的诱导和维持中的作用以及转化生长因子-β(TGF-β)对周细胞功能特性的影响。我们使用体外血脑屏障模型，通过将永生化的小鼠脑毛细血管内皮细胞(MBEC4)与大鼠脑周细胞的原代培养共培养而建立。与大鼠周细胞共培养可显著降低MBEC4细胞对荧光素钠的通透性和罗丹明123的积聚，提示脑周细胞可诱导和上调血脑屏障功能。大鼠脑周细胞表达转化生长因子-β1mRNA。抗转化生长因子-β1 L抗体(10mU g/ml)或转化生长因子-βI型受体拮抗剂(SB431542)(10mU/m l)处理细胞12h可显著抑制周细胞诱导的血脑屏障功能的增强，而转化生长因子-β1(1 ng/ml)作用12h可显著促进细胞的血脑屏障功能，这种促进作用可被SB431542阻断。这些发现表明，脑周细胞通过持续产生转化生长因子-β，促进血脑屏障功能的上调。(C)2005 Elsevier B.V.保留所有权利。
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.