GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy

Han, Mingyue; Yang, Zhi; Sayed, Danish; He, Minzhen; Gao, Shumin; Lin, Lin; Yoon, Seong Hun; Abdellatif, Maha

doi:10.1093/cvr/cvs001

Cited by 77 publications

(72 citation statements)

References 24 publications

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“…Emerging evidence has suggested that a number of miRNAs are important in the regulation of adipocyte differentiation, including the miR-143 (9) and miR-1792 clusters (10). miR-26b is an intronic miRNA encoded in the carboxy-terminal domain, RNA polymerase II, polypeptide A, small phosphatase 1 (CTDSP1) gene that is important in a variety of different diseases, including lung carcinoma, breast cancer and cardiac hypertrophy (11)(12)(13). However, there have been few studies investigating the role of miR-26b in obesity and insulin sensitivity.…”

Section: Introductionmentioning

confidence: 99%

Expression of microRNA-26b, an obesity-related microRNA, is regulated by free fatty acids, glucose, dexamethasone and growth hormone in human adipocytes

Xu¹,

Shi

et al. 2014

Molecular Medicine Reports

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Abstract. MicroRNAs (miRNAs) are short non-coding RNAs that are involved in numerous biological processes, including obesity and insulin resistance. miR-26b is an obesity-related intronic miRNA located in the intron of the carboxy-terminal domain, RNA polymerase II, polypeptide A, small phosphatase 1 gene. miR-26b is abundantly expressed in mice and mature human adipocytes, and is associated with the expression of adipokines. In the present study, the effects of energy-source materials and hormones associated with obesity, on miR-26b expression were investigated. It was demonstrated that free fatty acids (FFAs), glucose, glucocorticoids and growth hormone (GH) downregulate the expression of miR-26b in human adipocytes. The results indicate that the expression of miR-26b is affected by a variety of factors that are correlated with obesity and insulin sensitivity. Therefore, miR-26b may be an important mediator in the development of obesity-associated insulin resistance.

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Section: Introductionmentioning

confidence: 99%

Expression of microRNA-26b, an obesity-related microRNA, is regulated by free fatty acids, glucose, dexamethasone and growth hormone in human adipocytes

Xu¹,

Shi

et al. 2014

Molecular Medicine Reports

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“…miR-26b seems to be involved in cardiac hypertrophy by regulating GATA4, a transcription factor that increases alpha-skeletal actin and atrial natriuretic factor, 2 factors relevant for cardiac hypertrophy. 29,30 Recently, miR-26b was reported to be implicated in nitric oxide and atrial natriuretic peptide signaling in vascular smooth muscle cells. 40 In conclusion, the present study provides the first evidence of 3′-UTR-directed regulation of HSD11B2 mRNA by miRNAs.…”

Section: Discussionmentioning

confidence: 99%

Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by MicroRNA

et al. 2014

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Abstract-The enzyme 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is selectively expressed in aldosterone target tissues, conferring aldosterone selectivity for the mineralocorticoid receptor. A diminished activity causes salt-sensitive hypertension. The mechanism of the variable and distinct 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) expression in the cortical collecting duct is poorly understood. Here, we analyzed for the first time whether the 11β-HSD2 expression is modulated by microRNAs (miRNAs). In silico analysis revealed 53 and 27 miRNAs with potential binding sites on human or rat HSD11B2 3′-untranslated region. A reporter assay demonstrated 3′-untranslated region-dependent regulation of human and rodent HSD11B2. miRNAs were profiled from cortical collecting ducts and proximal convoluted tubules. Bioinformatic analyses showed a distinct clustering for cortical collecting ducts and proximal convoluted tubules with 53 of 375 miRNAs, where 13 were predicted to bind to the rat HSD11B2 3′-untranslated region. To gain insight into potentially relevant miRNAs in vivo, we investigated 2 models with differential 11β-HSD2 activity linked with saltsensitive hypertension.(1) Comparing Sprague-Dawley with low and Wistar rats with high 11β-HSD2 activity revealed rno-miR-20a-5p, rno-miR-19b-3p, and rno-miR-190a-5p to be differentially expressed. (2) Uninephrectomy lowered 11β-HSD2 activity in the residual kidney with differentially expressed rno-miR-19b-3p, rno-miR-29b-3p, and rnomiR-26-5p. In conclusion, miRNA-dependent mechanisms seem to modulate 11β-HSD2 dosage in health and disease The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl

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“…Primary cardiomyocyte culture, transfection, and immunofluorescence: Primary cardiomyocytes were isolated from neonatal C57Bl/6 mice 7) and cultivated in 6 well plates with Dulbecco's modified Eagle's medium (DMEM)/F12 supplemented with 110 U/mL penicillin, 100 μg/mL streptomycin, and 10% fetal bovine serum (Gibco) in humidified air (5% CO 2 ) at 37°C. For transfection or chemical treatments, cells were seeded into 6-well culture plates (5-10 × 10 4 cells/cm 2 ) and serumstarved for 18 hours, and either infected with lentivirus at a multiplicity of infection (MOI) of 100 or with cardiotrophin-1 (CT-1) (1nM), isoprenaline (ISO,10 μM) and leukemia inhibitory factor (LIF) (1000 U/mL) for 48-72 hours.…”

Section: Methodsmentioning

confidence: 99%

“…4,5) Increasing evidence has demonstrated dysregulated expression patterns of specific miRNAs could alter the cellular response of cardiomyocytes, leading to the pathology of cardiac concentric hypertrophy and heart failure. 2,[6][7][8] For example, miR-133 was down-modulated in hypertrophic human heart and played a role in HF via target genes RhoA, Cdc42 and Nelf-A/ WHSC2; 9) miR-195 transgenic mice showed pathological cardiac growth and heart failure; 3) and the transcription of miR23a was activated by nuclear factor of activated T cells (NFAT) whose hypertrophic effect was ascribed to miR-23a. 10) Previously we found some dysregulated miRNAs in failing human hearts caused by dilated cardiomyopathy, in which micrRNA-340-5p (miR-340) represented the most significant difference (2.6 fold upregulation).…”

mentioning

confidence: 99%

microRNA-340-5p Functions Downstream of Cardiotrophin-1 to Regulate Cardiac Eccentric Hypertrophy and Heart Failure via Target Gene Dystrophin

et al. 2015

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SummaryPathological cardiac hypertrophy inevitably leads to the unfavorable outcomes of heart failure (HF) or even sudden death. microRNAs are key regulation factors participating in many pathophysiological processes. Recently, we observed upregulation of microRNA-340-5p (miR-340) in failing human hearts because of dilated cardiomyopathy, but the functional consequence of miR-340 remains to be clarified.We transfected neonatal cardiomyocytes with miR-340 and found fetal gene expression including Nppa, Nppb and Myh7. We also observed eccentric hypertrophy development upon treatment which was analogous to the phenotype after cardiotrophin-1 (CT-1) stimulation. As a potent inducer of cardiac eccentric hypertrophy, treatment by IL-6 family members CT-1 and leukemia inhibitory factor (LIF) led to the elevation of miR-340. Knockdown of miR-340 using antagomir attenuated fetal gene expression and hypertrophy formation, which means miR-340 could convey the hypertrophic signal of CT-1. To demonstrate the initial factor of miR-340 activation, we constructed a volume overloaded abdominal aorta-inferior vena cava fistula rat HF model. miR-340 and CT-1 were found to be up-regulated in the left ventricle. Dystrophin (DMD), a putative target gene of miR-340 which is eccentric hypertrophy-susceptible, was decreased in this HF model upon Western blotting and immunohistochemistry tests. Luciferase assay constructed in two seed sequence of DMD gene 3'UTR showed decreased luciferase activities, and miR-340 transfected cells resulted in the degradation of DMD.miR-340 is a pro-eccentric hypertrophy miRNA, and its expression is dependent on volume overload and cytokine CT-1 activation. Cardiomyocyte structure protein DMD is a target of miR-340. (Int Heart J 2015; 56: 454-458)

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GATA4 expression is primarily regulated via a miR-26b-dependent post-transcriptional mechanism during cardiac hypertrophy

Abstract: Down-regulation of miR-26b in the heart is required for the up-regulation of GATA4 and the induction of pressure-induced cardiac hypertrophy. The results also underscore the functional relevance of miRNAs in regulating gene expression during cardiac hypertrophy.

Cited by 77 publications

References 24 publications

Expression of microRNA-26b, an obesity-related microRNA, is regulated by free fatty acids, glucose, dexamethasone and growth hormone in human adipocytes

Expression of microRNA-26b, an obesity-related microRNA, is regulated by free fatty acids, glucose, dexamethasone and growth hormone in human adipocytes

Regulation of 11β-Hydroxysteroid Dehydrogenase Type 2 by MicroRNA

microRNA-340-5p Functions Downstream of Cardiotrophin-1 to Regulate Cardiac Eccentric Hypertrophy and Heart Failure via Target Gene Dystrophin

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