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.

MicroRNAs from plants to animals, do they define a new messenger for communication?

“…With the discovery of circulating miRNAs in human body fluids, a more intricate level of cellular communication and regulation is introduced, and interactions between hormones and miRNAs are starting to emerge. Considering the significance of miRNAs and their involvement in various biological processes, it is not surprising that miRNAs are participating in the synthesis [ 181 , 182 ] and secretion [ 183 ] of several hormones. Likewise, the expression of several miRNAs is in turn under regulations of hormones.…”

The Role of DNMT and HDACs in the Fetal Programming of Hypertension by Glucocorticoids

“…Interestingly, changes in CA enzyme expression due to either epigenetic inhibitor only resulted in reduced PNMT and GR protein levels as TH and DBH remained elevated (Figures 6(a)-6(f)). Altered expression of miRNA may explain differences in gene and protein levels; indeed, miRNA have been shown to alter CA synthesis and secretion, and additional regulatory mechanisms are likely involved [33]. miRNA have also been shown to regulate corticosteroidogenesis [34] and dopamine synthesis [35] and transport [36] TH [37], SP1 [33], and GR levels [38].…”

Genome-wide profiling of microRNAs and prediction of mRNA targets in 17 bovine tissues

“…Significant differentially expressed (after corrected for multiple testing P-value <0.01 and absolute fold change >2) mature miRNAs were observed in all tissues except in black skin (Table 2; Figure 3A). Known miRNAs with high tissue-specificity showed significant differential expression in our analysis, such as miR-375 in adrenal gland (Ludwig et al 2016; Gai et al 2017), miR-219 in brain caudal lobe and brain cerebellum (Ludwig et al 2016), and miR-122 in liver (Jopling 2012; Szabo and Bala 2013; Modepalli et al 2014; Wang et al 2016a). No novel miRNAs were found to be up-regulated in any tissues, but some novel miRNAs were down-regulated in adrenal gland, brain cerebellum, lung, ovary, spleen and thyroid.…”