Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul, 137-701, Korea.
Histochem Cell Biol. 2014 Jan;141(1):33-42. doi: 10.1007/s00418-013-1134-5. Epub 2013 Aug 10.
Krüppel-like factor 4 (KLF4) is a transcription factor with diverse and cell type-specific functions and is associated with a variety of pathophysiological processes. Recently, it has been proposed that the regulation of KLF4 is critical to neuronal differentiation and that neural progenitors overexpressing KLF4 take on a glial identity. The present study aimed to determine whether KLF4 is involved in the astroglial reaction induced by ischemia-reperfusion injury in the brain. No specific KLF4 immunoreactivity was observed in resting astrocytes of the control hippocampus, but significant induction was detected in reactive astrocytes preferentially located in the CA1 and dentate hilar regions of the hippocampus following transient forebrain ischemia. Astroglial KLF4 expression was induced in the nuclei and cytoplasm within 3 days of ischemia and persisted for at least 4 weeks. This pattern was reproduced in an in vitro astrogliosis model of rat primary cortical astrocytes exposed to oxygen-glucose deprivation (OGD). Furthermore, immunoblot assay showed that nuclear and cytosolic extracts from cortical astrocytes subjected to OGD had significantly higher levels of KLF4 protein compared to normoxic extracts. Thus, our data demonstrate that KLF4 expression was induced in astroglia by ischemic injury both in vivo and in vitro, suggesting that KLF4 may act as a transcription factor linked to the regulation of the astroglial reaction following ischemic injury.
Krüppel 样因子 4（KLF4）是一种具有多种细胞类型特异性功能的转录因子，与多种病理生理过程有关。最近有人提出，KLF4 的调节对神经元分化至关重要，过表达 KLF4 的神经前体细胞具有神经胶质特性。本研究旨在确定 KLF4 是否参与脑缺血再灌注损伤引起的星形胶质细胞反应。在对照组海马体的静止星形胶质细胞中未观察到特定的 KLF4 免疫反应性，但在短暂性前脑缺血后，优先位于海马体 CA1 和齿状回区域的反应性星形胶质细胞中检测到明显的诱导。星形胶质细胞 KLF4 表达在缺血后 3 天内在细胞核和细胞质中诱导，并至少持续 4 周。在体外培养的大鼠皮质星形胶质细胞缺氧-葡萄糖剥夺（OGD）模型中也重现了这种模式。此外，免疫印迹分析显示，与正常氧提取液相比，OGD 处理的皮质星形胶质细胞的核和胞质提取物中 KLF4 蛋白水平显著升高。因此，我们的数据表明，KLF4 表达在体内和体外均由缺血性损伤诱导星形胶质细胞表达，提示 KLF4 可能作为一种转录因子，参与缺血性损伤后星形胶质细胞反应的调节。
