title: miR-375 negatively regulates the synthesis and secretion of catecholamines by targeting Sp1 in rat adrenal medulla.
abstract: The adrenal gland is an important endocrine gland in balancing homeostasis and the response to stress by synthesizing and secreting catecholamines (CATs), and it has been confirmed that microRNA-375 (miR-375) is highly expressed in adrenal medulla. However, up to now there are few reports about the functions and related mechanisms in adrenal medulla. The present study was thus designed to study the roles and related mechanisms in rat adrenal medulla. Our results showed that miR-375 was specifically expressed in rat adrenal medulla chromaffin cells, and its expression was downregulated when rats were exposed to stress. The further functional studies demonstrated that the inhibition of endogenous miR-375 induced the secretion of CATs in primary rat medulla chromaffin cells and PC12 cells, whereas miR-375 overexpression resulted in a decline of CAT secretion. In addition, our results showed that miR-375 negatively regulated tyrosine hydroxylase (TH) and dopamine-β-hydroxylase (DBH) and mediated adrenomedullary CAT biosynthesis. These functions of miR-375 were accomplished by its binding to the 3'-untranslated region of Sp1, which was involved in the regulation of TH and DBH expressions. These novel findings suggest that miR-375 acts as a potent negative mediator in regulating the synthesis and secretion of CATs in the adrenal medulla during the maintenance of homeostasis under stress.
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China; and.
authors.forename: Yedan
authors.initials: Y
authors.lastname: Gai
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China; and.
authors.forename: Jinglin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China; and.
authors.forename: Chao
authors.initials: C
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China; and.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: The 306th Hospital of People's Liberation Army, Beijing, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, People's Republic of China; and cuisheng@cau.edu.cn.
authors.forename: Sheng
authors.initials: S
authors.lastname: Cui
mesh_terms: D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism*; D019439:Chromaffin Cells / Q000378:metabolism*; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism; D015536:Down-Regulation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D016329:Sp1 Transcription Factor / Q000378:metabolism*; D014018:Tissue Distribution; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D002395:Catecholamines; C573498:MIRN376C microRNA, human; D035683:MicroRNAs; D016329:Sp1 Transcription Factor; D014446:Tyrosine 3-Monooxygenase; D004299:Dopamine beta-Hydroxylase
keywords: Sp1; catecholamines; miR-375; stress