MicroRNA profiling during mouse ventricular maturation: a role for miR-27 modulating Mef2c expression

Chinchilla, Ana; Lozano, Estefania; Daimi, Houria; Esteban, Francisco J.; Crist, Colin; Aránega, Amelia; Franco, Diego

doi:10.1093/cvr/cvq264

Cited by 101 publications

(100 citation statements)

References 36 publications

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“…Thus, additional studies are required to determine whether this slight derepression of PPAR-␥ by miR-27 inhibition contributes to the pro-angiogenic effects of the miR. Other potential targets contributing to the pro-angiogenic effect of miR-27 might be the lymphangiogenic growth factor VEGF-C, which is an in silico predicted target of miR-27, or the transcription factor MEF2C, which is targeted by miR-27 in cardiomyocytes 25 and regulates vascular integrity and angiogenesis. 50 Whereas VEGF-C was significantly up-regulated in antagomir-27a/btreated mice, the expression of MEF2C was not regulated.…”

Section: Discussionmentioning

confidence: 99%

“…24 The myocyte enhancer factor 2C (MEF2C) is another important target of miR-27b during heart development. 25 However, the specific functions and targets of miR-27 in endothelial cells are largely unexplored. As the family members miR-27a and miR-27b differ in only one nucleotide and share the same seed sequence, we investigated the specific role of both family members for the angiogenic activity of endothelial cells and determined the effects on neovascularization.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A

Urbich¹,

Kaluza²,

Frömel

et al. 2012

Blood

211

147

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IntroductionMicroRNAs (miRNAs) are highly conserved, single-stranded noncoding short RNA molecules (18-24 nucleotides) that regulate gene expression at the posttranscriptional level. miRNAs silence gene expression by inhibiting the translation of proteins from mRNAs or by promoting the degradation of mRNAs. After transcription of the primary miRNA transcripts from the genome, their maturation is mediated by the 2 RNase III endonucleases Dicer and Drosha. Then, mature miRNAs are incorporated into the RNA-induced silencing complex, 1 which mediates the binding of the miRNA to the 3Ј-untranslated region (3Ј-UTR) of the target mRNA leading either to translational repression or degradation of the target mRNA. 2 Because miRNAs control specific expression patterns of target genes, miRNAs represent attractive candidates to interfere with neovascularization.Increasing evidence indicates that miRNAs are important regulators of vascular development and angiogenesis. 3,4 In this context, first studies addressed the function of the miRNAprocessing enzymes Dicer and/or Drosha to explore the general role of miRNAs for angiogenesis. Depletion of Dicer in zebrafish or mice revealed an aberrant vessel growth, and silencing of Dicer in endothelial cells reduced in vitro angiogenesis. [5][6][7] To date, several miRs that regulate endothelial cell function and angiogenesis have been identified, 8 including the pro-angiogenic miRs miR-130a, 9 miR-210, 5,10,11 and miR-378. 12 In addition, miR-126 was shown to regulate vascular integrity and angiogenesis during development and in ischemia-induced angiogenesis. [13][14][15] In contrast, miR-221 and miR-222, 7,16 miR-15 and miR-16, 17,18 and members of the miR-17-92 cluster 19,20 inhibit angiogenesis.In our previous study, we found that the members of the miR-23ϳ27ϳ24 cluster, miR-27a and miR-27b, were highly expressed in endothelial cells. 6 In addition, miR-27b was downregulated after Dicer and Drosha silencing, and inhibition of miR-27b significantly reduced endothelial cell sprouting in vitro, 6 indicating that miR-27b exerts pro-angiogenic effects. Recently, Zhou et al demonstrated that the miR-23ϳ27ϳ24 cluster regulates angiogenesis. 21 In muscle stem cells, miR-27b down-regulates Pax3 expression during myogenic differentiation. 22 Moreover, miR-27 down-regulates Runx1 expression during granulocyte differentiation 23 and the nuclear receptor peroxisome proliferatoractivated receptor-␥ (PPAR-␥) in adipocytes. 24 The myocyte enhancer factor 2C (MEF2C) is another important target of miR-27b during heart development. 25 However, the specific functions and targets of miR-27 in endothelial cells are largely unexplored. As the family members miR-27a and miR-27b differ in only one nucleotide and share the same seed sequence, we investigated the specific role of both family members for the angiogenic activity of endothelial cells and determined the effects on neovascularization. Here we identified the angiogenesis inhibitor semaphorin 6A as a The online version of this article contains a ...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A

Urbich¹,

Kaluza²,

Frömel

et al. 2012

Blood

211

147

View full text Add to dashboard Cite

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“…Sequence analysis revealed two binding sites in miR-27b and the MCP1 3'-UTR. The literature reports that miR-27b affects the function of MCP1 by acting on certain target genes in myocardial cells (Chinchilla et al, 2011;Wang et al, 2012), but there have been no reports on whether miR-27b downregulates the expression of MCP1 and is involved in the occurrence and development of VMC. Therefore, in this study, we used IL-17 to induce the upregulation of MCP1 expression, then up-regulated the content of miR-27b by transiently transfecting H9C2 cells with miR-27b mimics.…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of microRNA-27b on interleukin 17 (IL-17)-induced monocyte chemoattractant protein-1 (MCP1) expression

et al. 2016

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ABSTRACT.We investigated the effect of microRNA-27b (miR-27b), a gene expression regulatory factor, on the expression of monocyte chemoattractant protein-1 (MCP1) stimulated by interleukin 17 (IL-17). After IL-17 had been added to H9C2 cardiomyocytes, an miR27b mimic was transfected into the H9C2 cells. The mRNA expression levels of miR-27b and MCP1 in the H9C2 cells were detected by SYBR green I fluorescence quantitative reverse transcription polymerase chain reaction. Enzyme-linked immunosorbent assay was used to measure the expression levels of MCP1 protein in the H9C2 cells. The expression of MCP1 mRNA in the H9C2 cells began to increase 2 h after IL-17 stimulation, reached a peak at 4 h, and then decreased. The MCP1 protein level increased gradually in the 24 h following IL-17 stimulation. After transfection with the miR-27b mimic, the expression of miR-27b in the H9C2 cells significantly increased than that in the miRNA negative control group (P < 0.01). The MCP1 mRNA and protein levels in the miR-27b mimic + IL-17 group were significantly reduced than that in the miRNA negative control + IL-17 group (P < 0.01). miR-27b inhibited IL-17-induced MCP1 expression in the H9C2

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“…The analysis of expression patterns for the Pitx2 isoforms during heart development has been characterized in zebrafish, chicken and mouse (Campione et al, 1999;Campione et al, 2001; Franco et al, 2003) These studies have pointed out that Pitx2c plays a determinant role in left-right signalling during cardiogenesis (Campione et al, 1999;Schweickert et al, 2000;Liu et al, 2001). In addition, a molecular 248 F. Hernandez-Torres et al link between Pitx2c and AF has been recently reported (Chinchilla et al, 2011;Kirchhof et al, 2011;Wang et al, 2010). Taken together, all these data suggest an important role of Pitx2c in heart development and homeostasis.…”

Section: Abstract: Pitx2 Isoforms Heart Development Mouse and Ventmentioning

confidence: 71%

“…In addition, we cannot rule out the possibility that different PITX2 isoforms could be coexpressed in the same cardiac cells, according to the fact that different isoforms of PITX2 can act together forming homo and heterodimers leading to transcriptional synergism (Cox et al, 2002;Saadi et al, 2003). Current studies suggest that Pitx2-mediated signalling during cardiogenesis is conducted within three different cell types: the myocardium, the cardiac neural crest (CNC) cells, and the pharyngeal arch mesenchyme (Campione et al, 1999;Chinchilla et al, 2011; Franco et al, 2003;Kioussi et al, 2002;Liu et al, 2002;Tessari et al, 2008), minimizing the possible role that Pitx2 a, b or c, may have during development of epicardial and endocardial derivatives. In addition, it was previously reported only that Pitx2c expression is never detected in endocardium (Liu et al, 2002).…”

mentioning

confidence: 99%

Expression patterns and immunohistochemical localization of PITX2B transcription factor in the developing mouse heart

Hernández-Torres

Franco²,

Aránega³

et al. 2015

Int. J. Dev. Biol.

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The Pitx2 gene is involved in the establishment of vertebrate left-right axis with an important role in subsequent heart organogenesis. Mutations in the Pitx2 gene have been associated with Axenfeld-Rieger syndrome, which is characterized by ocular, craniofacial, and umbilical anomalies, as well as cardiac defects. In addition, recent data have unravelled a molecular link between PITX2 loss of function and atrial fibrillation (AF), supporting an important role of Pitx2 not only in development but also in heart homeostasis. Three PITX2 isoforms have been described in mice: PITX2A, PITX2B, and PITX2C. During heart organogenesis, PITX2C seems to play a determinant role in left-right signalling from early somitogenesis onwards. However the participation of the PITX2A and/or PITX2B isoforms during cardiogenesis is controversial. Here we report for the first time that the Pitx2a and Pitx2b isoforms are jointly expressed with the Pitx2c isoform during heart development. Interestingly, in terms of relative quantification of mRNA, the Pitx2b and Pitx2c isoforms display similar expression profiles during cardiogenesis, decreasing with further development but maintaining their expression until adult stages. Moreover, a detailed analysis of PITX2B protein during cardiac development shows that PITX2B is dynamically expressed in the developing ventricular septum and asymmetrically expressed in the tricuspid valve primordia, suggesting a putative role of the PITX2B isoform during ventricular septation as well as in the maturation of the right portion of the atrioventricular canal. KEY WORDS: Pitx2 isoforms, heart development, mouse and ventricular septationThe Pitx2 gene is a member of the Bicoid-like homeobox family (Semina et al., 1996). During the last fifteen years several studies reported the implication of Pitx2 in the correct establishment of vertebrate left-right axis. Left-right asymmetry is established through a molecular cascade that gives rise to Pitx2 asymmetric expression in the Lateral Plate Mesoderm (LPM) at early stages of development (Logan et al., 1998). This expression determines left/right polarity of mesoderm-derived organs such as heart, gut, and stomach (Campione et al., 1999;Logan et al., 1998;Ryan et al., 1998;Yoshioka et al., 1998), supporting that Pitx2 could be the molecular transducer of embryonic left-right signalling at the organ level during early stages of development. Mutations in the Pitx2 gene have been associated with Axenfeld-Rieger syndrome, which is characterized by ocular, craniofacial, and umbilical anomalies (Semina et al., 1996) as well as cardiac defects, such as atrial septal defects, atrio-ventricular valve defects, and conduction Int. J. Dev. Biol. 59: 247-254 (2015) abnormalities (Cunningham et al., 1998;Mammi et al., 1998;Tsai, Grajewski, 1994).The Pitx2 gene is transcribed into three distinct isoforms in mice: Pitx2a, Pitx2b, and Pitx2c. Pitx2a and Pitx2b share the same promoter while Pitx2c uses an alternative promoter upstream of exon 4 (Gage et al., 1999;Schwei...

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MicroRNA profiling during mouse ventricular maturation: a role for miR-27 modulating Mef2c expression

Abstract: our data present a comprehensive profile of microRNA expression during ventricular maturation, providing an entry point for investigation of the functional roles of the most abundantly and differentially expressed microRNAs during cardiogenesis.

Cited by 101 publications

References 36 publications

MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A

MicroRNA-27a/b controls endothelial cell repulsion and angiogenesis by targeting semaphorin 6A

Inhibitory effect of microRNA-27b on interleukin 17 (IL-17)-induced monocyte chemoattractant protein-1 (MCP1) expression

Expression patterns and immunohistochemical localization of PITX2B transcription factor in the developing mouse heart

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