Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by MicroRNA

Rezaei, Mina; Andrieu, Thomas; Neuenschwander, Samuel; Bruggmann, Rémy; Mordasini, David; Frey, Felix J.; Vogt, Bruno; Frey, Brigitte M.

doi:10.1161/hypertensionaha.114.00002

Cited by 38 publications

(23 citation statements)

References 46 publications

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“…Lysine-specific demethylase 1 regulates histone methylation by demethylating histone H3 at lysine residues 4 and 9 and is involved in salt-sensitive hypertension (7, 8, 114, 118, 123). Certain miRs have been implicated in salt sensitivity and inverse salt sensitivity of blood pressure (114, 124–128). For example, miR-320 and miR-26b are increased in the aorta while miR-21 and miR-1331 are decreased in the aorta and myocardium, respectively, in Dahl salt-sensitive rats fed a high salt diet (125, 126).…”

Section: Gut Microbiota Epigenetics Hypertension and Salt Sensitivitymentioning

confidence: 99%

Gut microbiota in hypertension

José

Raj²

2015

Current Opinion in Nephrology and Hypertension

159

109

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Purpose of review Hypertension, which is present in about one quarter of the world’s population, is responsible for about 41% of the number one cause of death, cardiovascular disease. Not included in these statistics is the effect of sodium intake on blood pressure, even though an increase or a marked decrease in sodium intake can increase blood pressure. This review deals with the interaction of gut microbiota and the kidney with genetics and epigenetics in the regulation of blood pressure and salt sensitivity. Recent findings The abundance of the gut microbes, Firmicutes and Bacteroidetes, is associated with increased blood pressure in several models of hypertension, including the spontaneously hypertensive and Dahl salt-sensitive rats. Decreasing gut microbiota by antibiotics can increase or decrease blood pressure that is influenced by genotype. The biological function of probiotics may also be a consequence of epigenetic modification, related, in part, to microRNA. Products of the fermentation of nutrients by gut microbiota can influence blood pressure by regulating expenditure of energy, intestinal metabolism of catecholamines, and gastrointestinal and renal ion transport, and thus, salt sensitivity. Summary The beneficial or deleterious effects of gut microbiota on blood pressure is a consequence of several variables, including genetics, epigenetics, lifestyle, and intake of antibiotics. These variables may influence the ultimate level of blood pressure and control of hypertension.

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Section: Gut Microbiota Epigenetics Hypertension and Salt Sensitivitymentioning

confidence: 99%

Gut microbiota in hypertension

José

Raj²

2015

Current Opinion in Nephrology and Hypertension

159

109

View full text Add to dashboard Cite

show abstract

“…Several miRNAs have been shown to regulate gene expression or biological processes relevant to blood pressure regulation or the development of hypertension 2–6 and it is conceivable that many more miRNAs may be involved. It is, however, challenging to identify these miRNA-target relationships given the promiscuity of miRNA targeting and the uncertainty of target prediction.…”

Section: Introductionmentioning

confidence: 99%

Endogenous MicroRNAs in Human Microvascular Endothelial Cells Regulate mRNAs Encoded by Hypertension-Related Genes

et al. 2015

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The goal of the present study was to systematically identify endogenous microRNAs in endothelial cells that regulate mRNAs encoded by genes relevant to hypertension. Small RNA deep sequencing was performed in cultured human microvascular endothelial cells. Of the 50 most abundant microRNAs identified, 30 had predicted target mRNAs encoded by genes with known involvement in hypertension or blood pressure regulation. The cells were transfected with anti-miR oligonucleotides to inhibit each of the 30 microRNAs and the mRNA abundance of predicted targets was examined. Of 95 microRNA-target pairs examined, the target mRNAs were significantly up-regulated in 35 pairs and paradoxically down-regulated in 8 pairs. The result indicated significant suppression of the abundance of mRNA encoded by ADM by endogenous miR-181a-5p, ATP2B1 by the miR-27 family, FURIN by miR-125a-5p, FGF5 by the let-7 family, GOSR2 by miR-27a-3p, JAG1 by miR-21-5p, SH2B3 by miR-30a-5p, miR-98, miR-181a-5p, and the miR-125 family, TBX3 by the miR-92 family, ADRA1B by miR-22-3p, ADRA2A by miR-30a-5p and miR-30e-5p, ADRA2B by miR-30e-5p, ADRB1 by the let-7 family and miR-98, EDNRB by the miR-92 family, and NOX4 by the miR-92 family, miR-100-5p, and miR-99b-5p (n=3–9, P<0.05 vs. scrambled anti-miR). Treatment with anti-miR-21 decreased blood pressure in mice fed a 4% NaCl diet. Inhibition of the microRNAs targeting NOX4 mRNA increased H2O2 release from endothelial cells. The findings indicate widespread, tonic control of mRNAs encoded by genes relevant to blood pressure regulation by endothelial microRNAs and provide a novel and uniquely informative basis for studying the role of microRNAs in hypertension.

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“…As a miR‐17 family member, up‐regulation of miR‐20a‐5p was associated with advanced clinical stages of astrocytoma, indicating the potential of serum miR as the novel diagnostic and prognostic biomarkers for human astrocytoma . Comparing Sprague–Dawley with low and Wistar rats with high 11beta‐HSD2 activity revealed miR‐20a‐5p to be differentially expressed, suggesting that miR‐dependent mechanism seems to modulate 11beta‐HSD2 dosage in health and disease states . The fact that miR‐20a‐5p was significantly overexpressed in the HBV‐positive HCC patients compared with the HBV‐positive cancer‐free controls in both the training and validation sets indicated miR‐20a‐5p as a blood‐based early detection biomarker for HCC screening .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression

Fang

Guo

Cao

et al. 2016

J Cellular Molecular Medi

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Recently, it is implicated that aberrant expression of microRNAs (miRs) is associated with insulin resistance. However, the role of miR‐17 family in hepatic insulin resistance and its underlying mechanisms remain unknown. In this study, we provided mechanistic insight into the effects of miR‐20a‐5p, a member of miR‐17 family, on the regulation of AKT/GSK pathway and glycogenesis in hepatocytes. MiR‐20a‐5p was down‐regulated in the liver of db/db mice, and NCTC1469 cells and Hep1‐6 cells treated with high glucose, accompanied by reduced glycogen content and impaired insulin signalling. Notably, inhibition of miR‐20a‐5p significantly reduced glycogen synthesis and AKT/GSK activation, whereas overexpression of miR‐20a‐5p led to elevated glycogenesis and activated AKT/GSK signalling pathway. In addition, miR‐20a‐5p mimic could reverse high glucose‐induced impaired glycogenesis and AKT/GSK activation in NCTC1469 and Hep1‐6 cells. P63 was identified as a target of miR‐20a‐5p by bioinformatics analysis and luciferase reporter assay. Knockdown of p63 in the NCTC1469 cells and the Hep1‐6 cells by transfecting with siRNA targeting p63 could increase glycogen content and reverse miR‐20a‐5p inhibition‐induced reduced glycogenesis and activation of AKT and GSK, suggesting that p63 participated in miR‐20a‐5p‐mediated glycogenesis in hepatocytes. Moreover, our results indicate that p63 might directly bind to p53, thereby regulating PTEN expression and in turn participating in glycogenesis. In conclusion, we found novel evidence suggesting that as a member of miR‐17 family, miR‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression.

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Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by MicroRNA

Cited by 38 publications

References 46 publications

Gut microbiota in hypertension

Gut microbiota in hypertension

Endogenous MicroRNAs in Human Microvascular Endothelial Cells Regulate mRNAs Encoded by Hypertension-Related Genes

MicroRNA‐20a‐5p contributes to hepatic glycogen synthesis through targeting p63 to regulate p53 and PTEN expression

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