miR-375 mediates the CRF signaling pathway to regulate catecholamine biosynthesis by targeting Sp1 in porcine adrenal gland
miR-375 mediates the CRF signaling pathway to regulate catecholamine biosynthesis by targeting Sp1 in porcine adrenal gland
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miR-375介导CRF信号通路通过靶向猪肾上腺中的Sp1来调节儿茶酚胺生物合成
DOI：
10.1080/10253890.2018.1561845
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发表时间：
2019-02
影响因子：
2.3
通讯作者：
Cui S
中科院分区：
文献类型：
--
作者：
Wang Z;Gai Y;Zhou J;Liu J;Cui S
摘要促肾上腺皮质激素释放因子（CRF）是肾上腺中儿茶酚胺（CAT）生物合成的关键调节因子。此外，已经证实miR-375定位于小鼠肾上腺中。然而，miR-375和CRF在调节CATs生物合成中的关系仍有待建立。本研究旨在探讨CRF和miR-375在猪肾上腺CAT生物合成调控中的关系。8只成年雌性猪（4只对照; 4只脑室内注射50 μg CRF）用于本研究的体内实验。结果表明，miR-375仅定位于猪肾上腺髓质细胞。功能研究表明，miR-375通过影响CAT合成酶酪氨酸羟化酶（TH）、多巴胺β-羟化酶（DBH）和苯乙醇胺-N-甲基转移酶（PNMT）的表达来负调节原代细胞中CAT的合成。CRF在基础条件下和内源性miR-375抑制后上调原代肾上腺髓质细胞中CATs合成酶的表达;当通过转染miR-375-mic过表达细胞miR-375时，增强的作用消失。CRF在体内和体外均能降低miR-375的表达。我们的体外研究结果表明，CRF显著降低了miR-375的表达，可能是通过与CRFR 1结合。miR-375通过直接结合特异性蛋白1（Sp1）的3′-UTR区域发挥功能，Sp1参与调节Th和Dbh表达。这些数据共同表明，miR-375在调节CAT合成中起重要作用，并介导猪肾上腺髓质细胞中的CRF信号通路。
Abstract Corticotropin-releasing-factor (CRF) is a key regulator of catecholamines (CATs) biosynthesis in the adrenal gland. Furthermore, miR-375 has been confirmed to be localized in the mouse adrenal gland. However, the relationships between miR-375 and CRF in regulating CATs biosynthesis remain to be established. This study was designed to investigate the relationship between CRF and miR-375 in the regulation of CATs biosynthesis in the porcine adrenal gland. Eight adult female pigs (four controls; four injected intracerebroventricularly with 50 μg of CRF) were used for the in vivo experiments in this study. The results showed that miR-375 was exclusively localized in porcine adrenal medullary cells. Functional studies showed that miR-375 negatively regulated CATs synthesis in primary cells by affecting the expression of the CATs synthetases tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), and phenylethanolamine-N-methyltransferase (PNMT). CRF up-regulated the expression of CATs synthetase in primary adrenal medullary cells under basal conditions and upon endogenous miR-375 inhibition; the enhanced effects vanished when cellular miR-375 was overexpressed by transfecting miR-375-mic. CRF decreased the expression of miR-375 both in vivo and in vitro. Our in vitro results showed that CRF significantly decreased the expression of miR-375, perhaps by binding to CRFR1. miR-375 functions by directly binding to the 3′-UTR region of specificity protein 1 (Sp1), which is involved in regulating Th and Dbh expression. These data collectively indicate that miR-375 plays an important role in regulating CATs synthesis and mediates the CRF signaling pathway in porcine adrenal medullary cells.
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影响因子：
3.5
作者：
N. Vita;P. Laurent;S. Lefort;P. Chalon;J. Lelias;M. Kaghad;G. Le Fur;D. Caput;P. Ferrara
通讯作者：
N. Vita;P. Laurent;S. Lefort;P. Chalon;J. Lelias;M. Kaghad;G. Le Fur;D. Caput;P. Ferrara
影响因子：
14.9
作者：
Chen C;Ridzon DA;Broomer AJ;Zhou Z;Lee DH;Nguyen JT;Barbisin M;Xu NL;Mahuvakar VR;Andersen MR;Lao KQ;Livak KJ;Guegler KJ
通讯作者：
Guegler KJ
DOI：
10.1152/ajpregu.1987.253.2.r209
发表时间：
1987-08
期刊：
The American journal of physiology
影响因子：
--
作者：
W. Engeland;M. Lilly;T. Bruhn;D. Gann
通讯作者：
W. Engeland;M. Lilly;T. Bruhn;D. Gann
影响因子：
--
作者：
T. Teli;D. Markovic;M. Levine;E. Hillhouse;D. Grammatopoulos
通讯作者：
T. Teli;D. Markovic;M. Levine;E. Hillhouse;D. Grammatopoulos
影响因子：
4
作者：
Miki Miyajima;T. Numata;Moemi Minoshima;Masato Tanaka;R. Nishimura;T. Hosokawa;M. Kurasaki;T. Saito
通讯作者：
Miki Miyajima;T. Numata;Moemi Minoshima;Masato Tanaka;R. Nishimura;T. Hosokawa;M. Kurasaki;T. Saito