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转化生长因子-β1处理后大鼠脑周细胞、内皮细胞和星形胶质细胞系中基底膜相关分子的表达改变。

Altered expression of basement membrane-related molecules in rat brain pericyte, endothelial, and astrocyte cell lines after transforming growth factor-beta1 treatment.

作者信息

Kose Noriko, Asashima Tomoko, Muta Mariko, Iizasa Hisashi, Sai Yoshimichi, Terasaki Tetsuya, Nakashima Emi

机构信息

Department of Pharmaceutics, Kyoritsu University of Pharmacy, Tokyo, Japan.

出版信息

Drug Metab Pharmacokinet. 2007 Aug;22(4):255-66. doi: 10.2133/dmpk.22.255.

Abstract

The basement membrane at the blood-brain barrier (BBB) plays important roles in maintaining the structure and function of capillary vessels. The BBB is constructed from endothelial cells, astrocytes and pericytes, but their interactions in the formation or maintenance of basement membrane have not been established. Transforming growth factor-beta1 (TGF-beta1) is known to increase fibronectin in brain capillary basement membrane with deposition of beta-amyloid. We previously reported that the mRNA level of alpha-smooth muscle actin in a brain capillary pericyte cell line TR-PCT1 was increased by treatment with TGF-beta1. In this study, expression of mRNAs encoding basement membrane-related molecules in TR-PCT1, a rat endothelial cell line TR-BBB13, and a type 2 astrocyte cell line TR-AST4 was evaluated by RT-PCR. The effects of TGF-beta1 on expression of basement membrane-related genes in these cell lines were also examined. Fibronectin, MMP-9, tPA, TIMP-1, and PAI-l in TR-PCT1 were higher than in TR-BBB13 and TR-AST4. In TR-PCT1 treated with TGF-beta1, collagen type IV, PAI-1, and MMP-9 were increased, and TIMP-2 was reduced. The change in PAI-1 mRNA was faster than those in MMP-9, TIMP-2, collagen type IV mRNAs. These results suggest that pericytes may be key cells in the maintenance of the basement membrane at the BBB.

摘要

血脑屏障(BBB)处的基底膜在维持毛细血管的结构和功能方面发挥着重要作用。血脑屏障由内皮细胞、星形胶质细胞和周细胞构成,但其在基底膜形成或维持过程中的相互作用尚未明确。已知转化生长因子-β1(TGF-β1)会随着β-淀粉样蛋白的沉积增加脑毛细血管基底膜中的纤连蛋白。我们之前报道过,用TGF-β1处理大鼠脑毛细血管周细胞系TR-PCT1后,α-平滑肌肌动蛋白的mRNA水平会升高。在本研究中,通过逆转录聚合酶链反应(RT-PCR)评估了大鼠内皮细胞系TR-BBB13、2型星形胶质细胞系TR-AST4以及TR-PCT1中编码基底膜相关分子的mRNA的表达情况。还检测了TGF-β1对这些细胞系中基底膜相关基因表达的影响。TR-PCT1中的纤连蛋白、基质金属蛋白酶-9(MMP-9)、组织型纤溶酶原激活物(tPA)、金属蛋白酶组织抑制因子-1(TIMP-1)和纤溶酶原激活物抑制剂-1(PAI-1)高于TR-BBB13和TR-AST4。在用TGF-β1处理的TR-PCT1中,IV型胶原、PAI-1和MMP-9增加,而TIMP-2减少。PAI-1 mRNA的变化比MMP-9、TIMP-2、IV型胶原mRNA的变化更快。这些结果表明,周细胞可能是血脑屏障处基底膜维持的关键细胞。

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