Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21

Banjo, Toshihiro; Grajcarek, Janin; Yoshino, Daisuke; Osada, Hideto; Miyasaka, Kota; Kida, Yasuyuki S.; Ueki, Yosuke; Nagayama, Kazuaki; Kawakami, Koichi; Matsumotο, Takeo; Sato, Masaaki; Ogura, Toshihiko

doi:10.1038/ncomms2978

Cited by 84 publications

(70 citation statements)

References 60 publications

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“…During early looping, flow-mediated expression of the microRNA, miR-21 , is required for constriction of the region that will eventually become the AV valve [52]. In E9.5-12.5 hearts, mice lacking endocardial cilia ( Kif3a −/− embryos) exhibit abnormal cardiac cushion development [39].…”

Section: Mechanical Forces In Heart Developmentmentioning

confidence: 99%

Pulling on my heartstrings

McCormick

Tzima

2016

Current Opinion in Hematology

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Purpose of review Endothelial cells line the surface of the cardiovascular system and display a large degree of heterogeneity due to developmental origin and location. Despite this heterogeneity, all endothelial cells are exposed to wall shear stress (WSS) imparted by the frictional force of flowing blood, which plays an important role in determining the endothelial cell phenotype. Although the effects of WSS have been greatly studied in vascular endothelial cells, less is known about the role of WSS in regulating cardiac function and cardiac endothelial cells. Recent findings Recent advances in genetic and imaging technologies have enabled a more thorough investigation of cardiac hemodynamics. Using developmental models, shear stress sensing by endocardial endothelial cells has been shown to play an integral role in proper cardiac development including morphogenesis and formation of the conduction system. In the adult, less is known about hemodynamics and endocardial endothelial cells, but a clear role for WSS in the development of coronary and valvular disease is increasingly appreciated. Summary Future research will further elucidate a role for WSS in the developing and adult heart, and understanding this dynamic relationship may represent a potential therapeutic target for the treatment of cardiomyopathies.

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Section: Mechanical Forces In Heart Developmentmentioning

confidence: 99%

Pulling on my heartstrings

McCormick

Tzima

2016

Current Opinion in Hematology

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“…Physical stress can act as a “morphogen”; for example, shear stress and stretch of cardiomyocytes activate the differential expression of miR-21 during heart valve formation in zebrafish (Banjo et al 2013). Exposure of lake whitefish ( Coregonus lavaretus ) to microcystin significantly changed the expression of 6 liver miRNAs in a time-dependent manner (Brzuzan et al 2012), indicating the involvement of miRNAs at different levels of physiological acclimation responses.…”

Section: Response To Environmentmentioning

confidence: 99%

MicroRNA in Teleost Fish

Bizuayehu

Babiak

2014

Genome Biology and Evolution

179

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MicroRNAs (miRNAs) are transcriptional and posttranscriptional regulators involved in nearly all known biological processes in distant eukaryotic clades. Their discovery and functional characterization have broadened our understanding of biological regulatory mechanisms in animals and plants. They show both evolutionary conserved and unique features across Metazoa. Here, we present the current status of the knowledge about the role of miRNA in development, growth, and physiology of teleost fishes, in comparison to other vertebrates. Infraclass Teleostei is the most abundant group among vertebrate lineage. Fish are an important component of aquatic ecosystems and human life, being the prolific source of animal proteins worldwide and a vertebrate model for biomedical research. We review miRNA biogenesis, regulation, modifications, and mechanisms of action. Specific sections are devoted to the role of miRNA in teleost development, organogenesis, tissue differentiation, growth, regeneration, reproduction, endocrine system, and responses to environmental stimuli. Each section discusses gaps in the current knowledge and pinpoints the future directions of research on miRNA in teleosts.

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“…18 miR-21 has been shown to decrease apoptosis in varying cell types by directly targeting and suppressing Sprouty 2 which, in turn, negatively regulates Protein Kinase B (Akt) activation. 19–23 Additionally, Signal Transducer and Activator of Transcription 3 (STAT3) is a known regulator of miR-21. 24–28 After screening microRNAs and finding that miR-21 was downregulated following exposure to propofol, we hypothesized that the miR-21 signaling pathway (STAT3/Sprouty2/Akt) plays a role in the increased cell death observed in the hESC-derived neurons following propofol administration.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of MicroRNA-21 Is Involved in the Propofol-induced Neurotoxicity Observed in Human Stem Cell–derived Neurons

Twaroski

Yan²,

Olson³

et al. 2014

Anesthesiology

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Background Recent studies in various animal models have suggested that anesthetics such as propofol, when administered early in life, can lead to neurotoxicity. These studies have raised significant safety concerns regarding the use of anesthetics in the pediatric population and highlight the need for a better model by which to study anesthetic-induced neurotoxicity in humans. Human embryonic stem cells (hESCs) are capable of differentiating into any cell type and represent a promising model to study mechanisms governing anesthetic-induced neurotoxicity. Methods Cell death in hESC-derived neurons was assessed using TUNEL staining and microRNA (miR) expression was assessed using quantitative reverse transcription polymerase chain reaction (qRTPCR). miR-21 was overexpressed and knocked down using a miR-21 mimic and antagomir, respectively. Sprouty 2 was knocked down using a small interfering RNA and the expression of the miR-21 targets of interest was assessed by Western blot. Results Propofol dose and exposure time-dependently induced significant cell death (n = 3) in the neurons and downregulated several microRNAs, including miR-21. Overexpression of miR-21 and knockdown of Sprouty 2 attenuated the increase in TUNEL-positive cells following propofol exposure. In addition, miR-21 knockdown increased the number of TUNEL-positive cells by 30% (n = 5). Finally, activated Signal Transducer and Activator of Transcription 3 (STAT3) and protein kinase B (Akt) were downregulated and Sprouty 2 was upregulated following propofol exposure (n = 3). Conclusions These data suggest that: (1) hESC-derived neurons represent a promising in vitro human model for studying anesthetic-induced neurotoxicity, (2) propofol induces cell death in hESC-derived neurons and (3) the propofol-induced cell death may occur via a STAT3/miR-21/Sprouty2-dependent mechanism.

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Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21

Cited by 84 publications

References 60 publications

Pulling on my heartstrings

Pulling on my heartstrings

MicroRNA in Teleost Fish

Down-regulation of MicroRNA-21 Is Involved in the Propofol-induced Neurotoxicity Observed in Human Stem Cell–derived Neurons

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