Liu Xiaojuan, Yuan Damin, Nie Xiaoke, Shen Jianhong, Yan Yaohua, Zhang Dongmei, Gu Jianxin
Key Laboratory of Glycoconjugate Research, Ministry of Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Department of Pathogen Biology, Medical College, Nantong University, Nantong, Jiangsu, 226001, China.
J Mol Neurosci. 2015 Jan;55(1):206-216. doi: 10.1007/s12031-014-0305-8. Epub 2014 Apr 27.
Krüppel-like zinc-finger transcription factor 5 (KLF5), known as BTEB2 or IKLF, has several biological functions that involve cell proliferation, development and apoptosis. Previous studies demonstrated that BTEB2 had anti-apoptotic effect in multiple diseases such as esophageal cancer and non-small cell lung cancers (NSCLCs). However, the distribution and function of BTEB2 in CNS diseases remain unknown. In this study, we show that BTEB2 down-regulates neuronal apoptosis during pathophysiological processes of intracerebral hemorrhage (ICH). A rat ICH model was established by behavioral tests. Western blot and immunohistochemistry revealed a remarkable up-regulation of BTEB2 expression surrounding the hematoma after ICH. Double-labeled immunofluorescence showed BTEB2 was mostly co-localized with neurons, rarely with activated astrocytes and microglia. Furthermore, we detected that neuronal apoptosis marker active caspase-3 had co-localizations with BTEB2. In addition, KLF5 knockdown in vitro specifically resulted in increasing neuronal apoptosis coupled with reduced Bad phosphorylation at both ser112 and ser136 residues. All our findings suggested that BTEB2 down-regulated neuronal apoptosis via promoting Bad phosphorylation after ICH.
锌指蛋白转录因子5（Krüppel样因子5，KLF5），也被称为BTEB2或IKLF，具有多种生物学功能，涉及细胞增殖、发育和凋亡。先前的研究表明，BTEB2在多种疾病如食管癌和非小细胞肺癌（NSCLC）中具有抗凋亡作用。然而，BTEB2在中枢神经系统疾病中的分布和功能仍不清楚。在本研究中，我们发现BTEB2在脑出血（ICH）的病理生理过程中下调神经元凋亡。通过行为测试建立大鼠ICH模型。蛋白质免疫印迹法和免疫组织化学法显示，ICH后血肿周围BTEB2表达显著上调。双标免疫荧光显示，BTEB2主要与神经元共定位，很少与活化的星形胶质细胞和小胶质细胞共定位。此外，我们检测到神经元凋亡标志物活化的半胱天冬酶-3与BTEB2共定位。此外，体外敲低KLF5特异性导致神经元凋亡增加，同时ser112和ser136位点的Bad磷酸化减少。我们所有的研究结果表明，ICH后BTEB2通过促进Bad磷酸化下调神经元凋亡。
