内皮素-1 通过 ET 受体降低培养的大鼠星形胶质细胞中 Ephrin-A 和 B 亚型的表达。

Endothelin-1 decreases the expression of Ephrin-A and B subtypes in cultured rat astrocytes through ET receptors.

机构信息

Laboratory of Pharmacology, Kobe Pharmaceutical University, 4-19-1 Motoyama-Kita Higashinada, Kobe 668-8558 Japan.

出版信息

Neurosci Lett. 2021 Jan 10;741:135393. doi: 10.1016/j.neulet.2020.135393. Epub 2020 Dec 3.

DOI:10.1016/j.neulet.2020.135393

Abstract

Ephrin family proteins are cell surface molecules that regulate several cellular functions through cell-cell interactions. During nervous tissue repair after injury, the expression of ephrin subtypes in astrocytes is altered, affecting the axonal elongation and migration of neuronal precursors. However, the mechanism regulating the expression of ephrin subtypes in astrocytes has not been investigated. Herein, we studied the effects of endothelin-1 (ET-1) on the expression of ephrin subtypes in cultured rat astrocytes. Our results showed that ET-1 (100 nM) treatment for 1-24 h reduced the expression of ephrin-A2, -A4, -B2, and -B3 mRNA and protein in astrocytes, whereas the expression of ephrin-A1, -A3, -A5, and -B1 mRNA were not affected. Sarafotoxin S6c, a selective ET receptor agonist, decreased the expression of ephrin-A2, -A4, -B2, and -B3 in cultured astrocytes. The decrease in ephrin-A2, -A4, -B2, and -B3 expression by ET-1 treatment was reduced in the presence of BQ788, an ET receptor antagonist, while FR139317, an ET receptor antagonist, had no effects. These results suggest that ET-1 is a signaling molecule that downregulates ephrin-A2, -A4, -B2, and -B3 expression in astrocytes.

摘要

Ephrin 家族蛋白是细胞表面分子，通过细胞-细胞相互作用调节多种细胞功能。在损伤后神经组织修复过程中，星形胶质细胞中 Ephrin 亚型的表达发生改变，影响神经元前体细胞的轴突伸长和迁移。然而，调节星形胶质细胞中 Ephrin 亚型表达的机制尚未得到研究。在此，我们研究了内皮素-1 (ET-1) 对培养的大鼠星形胶质细胞中 Ephrin 亚型表达的影响。结果表明，ET-1（100 nM）处理 1-24 h 可降低星形胶质细胞中 Ephrin-A2、-A4、-B2 和 -B3 mRNA 和蛋白的表达，而 Ephrin-A1、-A3、-A5 和 -B1 mRNA 的表达不受影响。选择性 ET 受体激动剂 Sarafotoxin S6c 降低了培养的星形胶质细胞中 Ephrin-A2、-A4、-B2 和 -B3 的表达。ET 受体拮抗剂 BQ788 可减少 ET-1 处理对 Ephrin-A2、-A4、-B2 和 -B3 表达的降低，而 ET 受体拮抗剂 FR139317 则无此作用。这些结果表明，ET-1 是一种信号分子，可下调星形胶质细胞中 Ephrin-A2、-A4、-B2 和 -B3 的表达。