Koyama Yutaka, Yoshioka Yasuhiro, Matsuda Toshio, Baba Akemichi
Laboratory of Molecular Neuropharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Glia. 2003 Aug;43(2):185-9. doi: 10.1002/glia.10240.
When the brain is damaged, astrocytes often cause hyperplasia resulting in glial scar formation at the injured sites. Endothelins (ETs) have been shown to be involved in the pathophysiologic responses of astrocytes, including proliferation. In this study, we examined the mechanisms underlying the ET-induced astrocytic G1/S-phase cell cycle transition by focusing on focal adhesion kinase (FAK). A transient transfection with wild-type FAK was followed by an increase in bromodeoxyuridine (BrdU) incorporation into cultured rat astrocytes. The increases in BrdU incorporation induced by 100 nM ET-1 were not found in astrocytes transfected with dominant-negative FAK mutants (FRNK and dC14-FAK). The increases in BrdU incorporation induced by 10 nM phorbol 12-myristate 13-acetate (PMA) were not affected by the FAK mutants. Wild-type FAK did not induce stress fiber formation in cultured astrocytes. The dominant negative FAK mutant dC14-FAK did not prevent ET-induced astrocytic stress fiber formation. These results suggest that FAK mediated the astrocytic G1/S cell cycle transition induced by ET-1 downstream of the cytoskeletal actin reorganization.
当大脑受损时，星形胶质细胞常导致增生，在损伤部位形成胶质瘢痕。内皮素（ETs）已被证明参与星形胶质细胞的病理生理反应，包括增殖。在本研究中，我们通过聚焦粘着斑激酶（FAK）来研究ET诱导星形胶质细胞G1/S期细胞周期转变的机制。用野生型FAK进行瞬时转染后，培养的大鼠星形胶质细胞中溴脱氧尿苷（BrdU）掺入增加。在用显性负性FAK突变体（FRNK和dC14-FAK）转染的星形胶质细胞中未发现100 nM ET-1诱导的BrdU掺入增加。10 nM佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的BrdU掺入增加不受FAK突变体影响。野生型FAK未在培养的星形胶质细胞中诱导应力纤维形成。显性负性FAK突变体dC14-FAK不能阻止ET诱导的星形胶质细胞应力纤维形成。这些结果表明，FAK在细胞骨架肌动蛋白重组下游介导了ET-1诱导的星形胶质细胞G1/S细胞周期转变。
