Ke Kaifu, Song Yan, Shen Jiabing, Niu Mu, Zhang Haiyan, Yuan Daming, Ni Haidan, Zhang Yu, Liu Xiaorong, Dai Aihua, Cao Maohong
Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
Cell Mol Neurobiol. 2015 Apr;35(3):345-354. doi: 10.1007/s10571-014-0130-1. Epub 2014 Nov 5.
The novel Krüppel-like zinc finger protein Gli-similar 2 (Glis2), one member of the transcription factors, is involved in controlling the flow of genetic information and the modulation of diverse cellular activities. Accumulating evidence has demonstrated its important roles in adult development and several diseases. However, information regarding the regulation and possible function of Glis2 in the central nervous system is still limited. In this study, we explored the roles of Glis2 during the pathophysiological process of intracerebral hemorrhage (ICH). An ICH rat model was established and assessed by behavioral tests. Expression of Glis2 was significantly up-regulated in brain areas surrounding the hematoma following ICH. Immunofluorescence showed that Glis2 was strikingly increased in neurons, but not astrocytes or microglia. Up-regulation of Glis2 was found to be accompanied by the increased expression of active caspase-3 and Bax and decreased expression of Bcl-2 in vivo and vitro studies. Moreover, knocking down Glis2 by RNA-interference in PC12 cells reduced active caspase-3 and Bax expression while increased Bcl-2. Collectively, we speculated that Glis2 might exert pro-apoptotic function in neurons following ICH.
新型Krüppel样锌指蛋白Gli-相似蛋白2（Glis2）是转录因子的一员，参与控制遗传信息的传递以及多种细胞活动的调节。越来越多的证据表明其在成年发育和多种疾病中发挥重要作用。然而，关于Glis2在中枢神经系统中的调控及可能功能的信息仍然有限。在本研究中，我们探讨了Glis2在脑出血（ICH）病理生理过程中的作用。建立了ICH大鼠模型并通过行为测试进行评估。ICH后血肿周围脑区Glis2的表达显著上调。免疫荧光显示，Glis2在神经元中显著增加，但在星形胶质细胞或小胶质细胞中未增加。体内和体外研究均发现，Glis2的上调伴随着活性半胱天冬酶-3和Bax表达的增加以及Bcl-2表达的降低。此外，在PC12细胞中通过RNA干扰敲低Glis2可降低活性半胱天冬酶-3和Bax的表达，同时增加Bcl-2的表达。总体而言，我们推测Glis2可能在ICH后神经元中发挥促凋亡作用。
