Transcription factor CREB3L1 mediates cAMP and glucocorticoid regulation of arginine vasopressin gene transcription in the rat hypothalamus.
Transcription factor CREB3L1 mediates cAMP and glucocorticoid regulation of arginine vasopressin gene transcription in the rat hypothalamus.
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DOI：
10.1186/s13041-015-0159-1
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发表时间：
2015-10-26
期刊：
影响因子：
3.6
通讯作者：
Murphy D
中科院分区：
文献类型：
--
作者：
Greenwood M;Greenwood MP;Mecawi AS;Loh SY;Rodrigues JA;Paton JF;Murphy D
精氨酸加压素（AVP）是一种神经肽激素，通过控制肾脏对水的重吸收来调节水的稳态，由下丘脑视上核和室旁核合成。血浆渗透压的增加刺激AVP分泌到血液循环中并诱导这些核中的AVP合成。尽管下丘脑AVP转录调控机制的研究表明cAMP和糖皮质激素分别正性和负性调节AVP的表达，但其分子机制仍不清楚。最近，我们确定CREB3L1（cAMP反应元件结合蛋白3样1）作为一个假定的转录因子的Avp转录在大鼠下丘脑。然而，CREB 3L1在高渗应激反应中的调节机制尚未见报道。本研究旨在探讨AVP转录调控因子cAMP和糖皮质激素对转录因子CREB 3L1的影响，为cAMP和糖皮质激素影响AVP表达提供分子机制。在AtT20细胞和下丘脑器官型培养物中研究cAMP和糖皮质激素处理对Creb3l1的影响。通过用毛喉素处理，Creb3l1的表达在mRNA和蛋白质水平上都增加，这提高了细胞内cAMP水平。毛喉素激活cAMP也增加了AtT20细胞中Avp启动子的活性，这种作用被shRNA介导的Creb3l1沉默所减弱。毛喉素诱导的Creb3l1表达的增加与地塞米松联合治疗减少，在体内，腹腔注射地塞米松钝化Creb3l1和Avp表达的增加由高渗应激诱导。在这里，我们表明，cAMP和糖皮质激素正，负调节Creb3l1在大鼠下丘脑的表达，分别和cAMP对AVP表达的调节是通过CREB3L1介导。这些数据提供了CREB 3L1，一个新发现的AVP表达的转录因子，与先前提出的Avp转录机制，扩展了我们的理解Avp在下丘脑的转录调控之间的连接。
Arginine vasopressin (AVP), a neuropeptide hormone that functions in the regulation of water homeostasis by controlling water re-absorption at kidneys, is synthesised in supraoptic nucleus and paraventricular nucleus of the hypothalamus. An increase in plasma osmolality stimulates secretion of AVP to blood circulation and induces AVP synthesis in these nuclei. Although studies on mechanism of AVP transcriptional regulation in hypothalamus proposed that cAMP and glucocorticoids positively and negatively regulate Avp expression, respectively, the molecular mechanisms have remained elusive. Recently, we identified CREB3L1 (cAMP-responsive element binding protein 3 like 1) as a putative transcription factor of Avp transcription in the rat hypothalamus. However the mechanism of how CREB3L1 is regulated in response of hyperosmotic stress in the neurons of hypothalamus has never been reported. This study aims to investigate effect of previously reported regulators (cAMP and glucocorticoid) of Avp transcription on transcription factor CREB3L1 in order to establish a molecular explanation for cAMP and glucocorticoids effect on AVP expression. The effect of cAMP and glucocorticoid treatment on Creb3l1 was investigated in both AtT20 cells and hypothalamic organotypic cultures. The expression of Creb3l1 was increased in both mRNA and protein level by treatment with forskolin, which raises intracellular cAMP levels. Activation of cAMP by forskolin also increased Avp promoter activity in AtT20 cells and this effect was blunted by shRNA mediated silencing of Creb3l1. The forskolin induced increase in Creb3l1 expression was diminished by combined treatment with dexamethasone, and, in vivo, intraperitoneal dexamethasone injection blunted the increase in Creb3l1 and Avp expression induced by hyperosmotic stress. Here we shows that cAMP and glucocorticoid positively and negatively regulate Creb3l1 expression in the rat hypothalamus, respectively, and regulation of cAMP on AVP expression is mediated through CREB3L1. This data provides the connection between CREB3L1, a newly identified transcription factor of AVP expression, with the previously proposed mechanism of Avp transcription which extends our understanding in transcription regulation of Avp in the hypothalamus.
影响因子：
2.5
作者：
Arima H;Baler R;Aguilera G
通讯作者：
Aguilera G