Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells.
Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells.
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Orexin A在小鼠促肾上腺皮质激素AtT20细胞中增强BMP-4调控的促肾上腺皮质激素原转录
DOI：
10.3390/ijms22094553
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发表时间：
2021-04-27
影响因子：
5.6
通讯作者：
Otsuka F
中科院分区：
文献类型：
--
作者：
Fujisawa S;Komatsubara M;Tsukamoto-Yamauchi N;Iwata N;Nada T;Wada J;Otsuka F
食欲素主要在下丘脑中表达，并且已知激活下丘脑-垂体-肾上腺（HPA）轴，该轴参与各种应激反应及其恢复力。然而，食欲素对垂体促肾上腺皮质激素细胞内分泌功能的影响尚不清楚。在这项研究中，我们调查的作用，食欲素A在前阿黑皮素（POMC）转录使用小鼠促肾上腺皮质激素AtT 20细胞，专注于骨形态发生蛋白（BMP）系统在垂体中表达。关于食欲素的受体，2型（OXR 2）而不是1型（OX 1 R）受体mRNA主要在AtT 20细胞中表达。结果发现，食欲素A治疗增强POMC的表达，诱导促肾上腺皮质激素释放激素（CRH）刺激通过上调CRH受体1型（CRHR 1）。Orexin A对BMP-4处理抑制的POMC转录没有直接影响，但它抑制BMP-4诱导的Smad 1/5/9磷酸化和Id-1 mRNA表达。进一步揭示，食欲素A对AtT 20细胞中I型和II型BMP受体的表达水平没有显著影响，但上调抑制性Smad 6/7 mRNA和蛋白水平。结果表明，食欲素A上调CRHR信号和下调BMP-Smad信号，导致促皮质细胞POMC转录的增强。
Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic–pituitary–adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells.
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影响因子：
5.2
作者：
Inutsuka A;Yamanaka A
通讯作者：
Yamanaka A
影响因子：
5.8
作者：
Blanco, M;López, M;Beiras, A
通讯作者：
Beiras, A
影响因子：
--
作者：
Kodadek T;Cai D
通讯作者：
Cai D
影响因子：
4.8
作者：
Aoki, Y;Iwasaki, Y;Saito, H
通讯作者：
Saito, H
影响因子：
3.2
作者：
Jászberényi, M;Bujdosó, E;Telegdy, G
通讯作者：
Telegdy, G