Role of GATA-6 and Bone Morphogenetic Protein-2 in Dexamethasone-Induced Cleft Palate Formation in Institute of Cancer Research Mice
Role of GATA-6 and Bone Morphogenetic Protein-2 in Dexamethasone-Induced Cleft Palate Formation in Institute of Cancer Research Mice
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GATA-6 和骨形态发生蛋白 2 在地塞米松诱导的癌症研究所小鼠腭裂形成中的作用
DOI：
10.1097/scs.0000000000002844
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发表时间：
2016-09-01
影响因子：
0.9
通讯作者：
Rong, Li
中科院分区：
文献类型：
--
作者：
Lan, Shi-Jie;Yang, Xiao-Guang;Rong, Li
地塞米松诱导腭裂的机制尚不完全清楚。骨形态发生蛋白-2（BMP-2）与地塞米松诱导的骨质疏松症有关。在本研究中，作者通过地塞米松诱导癌症研究所小鼠腭裂模型来研究BMP-2及其转录元件加塔-6的作用。作者将不同剂量的地塞米松注射到妊娠小鼠（E13）中，并评估腭架的组织学和BMP-2，加塔-6和特定的腭突相关蛋白的表达水平。结果表明，腭裂的发生与地塞米松剂量有关，高剂量组（50 mg/kg）腭裂发生率（50.55%）高于低剂量组（6 mg/kg）（38.10%）。 透射电子显微镜观察显示，腭裂患者的腭架出现了明显的细胞变化，包括细胞连接松散、细胞肿胀以及细胞外基质和线粒体减少。地塞米松处理后，腭部细胞凋亡率随剂量增加而增加。Western blotting分析显示，加塔-6和BMP-2的表达水平降低，而凋亡蛋白bax和caspase-3的表达水平升高。作者的研究结果表明地塞米松诱导的腭裂形成与细胞凋亡有关，并呈剂量依赖性。BMP-2和加塔-6介导地塞米松诱导的腭裂形成。
AbstractThe mechanism of cleft palate induction by dexamethasone is not fully known. Bone morphogenetic protein-2 (BMP-2) has been associated with dexamethasone-induced osteoporosis. In this study, the authors induced cleft palate models in Institute of Cancer Research mice by dexamethasone to investigate the role of BMP-2 and its transcriptional element GATA-6. The authors injected different doses of dexamethasone into pregnant mice (E13), and assessed the histology of the palatal shelf and the expression levels of BMP-2, GATA-6, and specific apoptosis-related proteins. The results showed that cleft palate formation was dependent on dexamethasone dosage, with high incidence (50.55%) at high concentration (50 mg/kg) compared with the low doses (6 mg/kg, 38.10%). Transmission electron microscopy revealed significant cellular changes of the cleft palate shelf, including loose cell connection, cellular swelling, as well as reduced extracellular matrix and mitochondria. Following exposure to dexamethasone, the apoptotic rate in the palate increased with elevated dosage. Western blotting analysis indicated that the expression levels of GATA-6 and BMP-2 were reduced, while the levels of apoptotic proteins bax and caspase-3 were increased. The results of authors’ study suggested that dexamethasone-induced cleft palate formation involved apoptosis occurred in a dose-dependent manner. BMP-2 and GATA-6 mediated dexamethasone-induced cleft palate formation.