Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways

Crippa, Stefania; Nemir, Mohamed; Ounzain, Samir; Ibberson, Mark; Berthonneche, Corinne; Sarre, Alexandre; Boisset, Gaëlle; Maison, Damien; Harshman, Keith; Xénarios, Ioannis; Diviani, Dario; Pedrazzini, Thierry

doi:10.1093/cvr/cvw031

Cited by 38 publications

(40 citation statements)

References 72 publications

(86 reference statements)

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“… 194 This is in part regulated by decreased microRNAs (miR) such as miR26a, providing a link to cardiac injury. 195 Similar regulatory properties have been attributed to other miRs expressed in the AT and cardiovascular system. 49 , 196–199 The inflammatory nature of epicardial AT has been known for years, 200 and is supported by numerous molecular mechanisms.…”

Section: Ectopic Fat Depots and Chronic Inflammationmentioning

confidence: 58%

The role of infiltrating immune cells in dysfunctional adipose tissue

Guzik

Skiba

Touyz

et al. 2017

Cardiovascular Research

333

233

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Adipose tissue (AT) dysfunction, characterized by loss of its homeostatic functions, is a hallmark of non-communicable diseases. It is characterized by chronic low-grade inflammation and is observed in obesity, metabolic disorders such as insulin resistance and diabetes. While classically it has been identified by increased cytokine or chemokine expression, such as increased MCP-1, RANTES, IL-6, interferon (IFN) gamma or TNFα, mechanistically, immune cell infiltration is a prominent feature of the dysfunctional AT. These immune cells include M1 and M2 macrophages, effector and memory T cells, IL-10 producing FoxP3+ T regulatory cells, natural killer and NKT cells and granulocytes. Immune composition varies, depending on the stage and the type of pathology. Infiltrating immune cells not only produce cytokines but also metalloproteinases, reactive oxygen species, and chemokines that participate in tissue remodelling, cell signalling, and regulation of immunity. The presence of inflammatory cells in AT affects adjacent tissues and organs. In blood vessels, perivascular AT inflammation leads to vascular remodelling, superoxide production, endothelial dysfunction with loss of nitric oxide (NO) bioavailability, contributing to vascular disease, atherosclerosis, and plaque instability. Dysfunctional AT also releases adipokines such as leptin, resistin, and visfatin that promote metabolic dysfunction, alter systemic homeostasis, sympathetic outflow, glucose handling, and insulin sensitivity. Anti-inflammatory and protective adiponectin is reduced. AT may also serve as an important reservoir and possible site of activation in autoimmune-mediated and inflammatory diseases. Thus, reciprocal regulation between immune cell infiltration and AT dysfunction is a promising future therapeutic target.

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Section: Ectopic Fat Depots and Chronic Inflammationmentioning

confidence: 58%

The role of infiltrating immune cells in dysfunctional adipose tissue

Guzik

Skiba

Touyz

et al. 2017

Cardiovascular Research

333

233

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“…To date, several miRNAs that control expression of genes involved in cell cycle progression have been identified. Interestingly, changes triggered in response to injury in zebrafish are not conserved in mammals, suggesting that miRNA expression contributes to the high regenerative capacity of the zebrafish heart (Aguirre et al., ; Crippa et al., ). While miRNAs represent an attractive therapeutic target, we must first understand when and where specific miRNAs are required to facilitate regeneration.…”

Section: Dynamics Of Zebrafish Heart Regenerationmentioning

confidence: 99%

Zebrafish heart regeneration: 15 years of discoveries

2017

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Cardiovascular disease is the leading cause of death worldwide. Compared to other organs such as the liver, the adult human heart lacks the capacity to regenerate on a macroscopic scale after injury. As a result, myocardial infarctions are responsible for approximately half of all cardiovascular related deaths. In contrast, the zebrafish heart regenerates efficiently upon injury through robust myocardial proliferation. Therefore, deciphering the mechanisms that underlie the zebrafish heart's endogenous regenerative capacity represents an exciting avenue to identify novel therapeutic strategies for inducing regeneration of the human heart. This review provides a historical overview of adult zebrafish heart regeneration. We summarize 15 years of research, with a special focus on recent developments from this fascinating field. We discuss experimental findings that address fundamental questions of regeneration research. What is the origin of regenerated muscle? How is regeneration controlled from a genetic and molecular perspective? How do different cell types interact to achieve organ regeneration? Understanding natural models of heart regeneration will bring us closer to answering the ultimate question: how can we stimulate myocardial regeneration in humans?

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“…Again, the miR-133b could be a key miR because of its direct control on the CTGF protein, necessary to regulate the transition in endocardial cells from epithelial to mesenchymal elements. Although different patterns of miR expression are found by transcriptome analyses during regeneration, miR-1 and miRs-133a/b seem to be commonly expressed in mammals as well as in zebrafish 53 . This study provides key clues for the experimental early activation of pro-regenerative responses in the heart of the zebrafish, and provides crucial insights for the development of therapies targeting heart disease.…”

Section: Discussionmentioning

confidence: 92%

Micro RNAs are involved in activation of epicardium during zebrafish heart regeneration

Ceci

Carlantoni

Missinato

et al. 2018

Cell Death Discovery

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Zebrafish could be an interesting translational model to understand and improve the post-infarction trial and possible regeneration in humans. The adult zebrafish is able to regenerate efficiently after resecting nearly 20% of the ventricular apex. This process requires the concert activation of the epicardium and endocardium, as well as trans-differentiation of pre-existing cardiomyocytes that together replace the lost tissue. The molecular mechanisms involved in this activation process are not completely clarified. In this work, in order to investigate if the downregulation of these miRNAs (miRs) are linked with the activation of epicardium, the expressions of miR-133a, b and miR-1 during regeneration were analysed. qPCR analyses in whole-heart, or from distinct dissected epicardial cells comparing to regenerative clot (containing cardiomyocytes, fibroblasts and endocardial cells) by a laser-micro-dissector, have indicated that already at 24 h there is a downregulation of miRs: (1) miR-133a and miR-1 in the epicardium and (2) miR-133b and miR-1 in the regenerative clot. All the miRs remain downregulated until 7 days post-surgery. With the aim to visualize the activations of heart component in combination with miRs, we developed immunohistochemistry using antibodies directed against common markers in mammals as well as zebrafish: Wilms tumour 1 (WT1), a marker of epicardium; heat-shock protein 70 (HSP70), a chaperon activated during regeneration; and the Cardiac Troponin T (cTnT), a marker of differentiated cardiomyocytes. All these markers are directly or indirectly linked to the investigated miRs. WT1 and HSP70 strongly marked the regeneration site just at 2–3 days postventricular resection. In coherence, cTnT intensively marked the regenerative portion from 7 days onwards. miRs-1 and -133 (a,b) have been strongly involved in the activation of epicardium and regenerative clot during the regeneration process in zebrafish. This study can be a useful translational model to understand the early epicardial activation in which miRs-133a and miR-1 seem to play a central role as observed in the human heart.

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Comparative transcriptome profiling of the injured zebrafish and mouse hearts identifies miRNA-dependent repair pathways

Cited by 38 publications

References 72 publications

The role of infiltrating immune cells in dysfunctional adipose tissue

The role of infiltrating immune cells in dysfunctional adipose tissue

Zebrafish heart regeneration: 15 years of discoveries

Micro RNAs are involved in activation of epicardium during zebrafish heart regeneration

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