Knockdown of miR-26a in zebrafish leads to impairment of the anti-inflammatory function of TnP in the control of neutrophilia

Falcão, Maria Alice Pimentel; Walker, Cristiani Isabel Banderó; Disner, Geonildo Rodrigo; Batista-Filho, João; Soares, Amanda Beatriz Silva; Balan-Lima, Leticia; Lima, Carla; Lopes-Ferreira, Mônica

doi:10.1016/j.fsi.2021.04.029

Cited by 8 publications

(10 citation statements)

References 39 publications

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“…Recent studies have taken advantage of their convenient embryology, ease of genetic manipulation and conserved evolutionary biology to obtain important information in the field of inflammation research. 6 Many of these strengths as a genetic model are also directly useful in pharmacological research. The focus of our research at the Butantan Institute is to identify candidate therapeutic targets in inflammatory processes by using molecules and toxins from venomous fish.…”

Section: The 'Plataforma Zebrafish Open Doors' Programmementioning

confidence: 99%

“…1 In addition, the zebrafish genome has been fully sequenced, revealing 70% similarity to human genes in general, and 84% homology of genes known to be associated with human disease that have a zebrafish counterpart. 2 Since the zebrafish was first employed by George Streisinger in the early 1980s in genetic and developmental biology studies, [3][4][5] it has become a prominent organism for understanding the role of leukocytes in the control of sterile or microbe-induced inflammation, 6 for modelling several human diseases, and as a test system in pharmacological studies, 5,7,8 contributing to toxicological/teratological evaluations and preclinical drug discovery. 9,10 Zebrafish embryos are not covered by the strict regulatory frameworks that are associated with animal experimentation, and as such they can be considered replacement or refinement methods.…”

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confidence: 99%

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Zebrafish Beyond the Bench: The ‘Plataforma Zebrafish Open Doors’ Programme

et al. 2021

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The Butantan Institute is a pioneering Brazilian health sciences institution, which also houses a large science park with museums that contribute to ongoing science education for schools and the wider community. In recent years, as part of Butantan Institute’s Plataforma Zebrafish™, zebrafish embryos have been used for the dissemination of scientific knowledge during on-site events and as part of outreach campaigns to non-scientific audiences, mostly children. The aim of this work is mainly to demystify the activities of the scientific researcher, highlight the role of science in the furthering of knowledge, and increase public interest and confidence in science. In this article, the Institute’s ‘Plataforma Zebrafish Open Doors’ programme is described, which offered guided tours of the laboratory facilities. The tours gave visitors the opportunity to observe zebrafish research and embryo development, and to use the knowledge gained from this experience as a framework for understanding fundamental ethical issues. During the 2-day event, around 800 visitors (most of them school-age children) attended. Together with the guided tours, our experience of outreach offered meaningful opportunities to bring children and members of the public closer to science and ‘real-life’ scientists, hopefully inspiring and encouraging the next generation of scientists. It also gave the scientists an opportunity to engage more closely with wider society. We believe that these activities also substantially contribute to the wider dissemination of relevant experimental results that have been obtained with public funding and that impact society in general.

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Section: The 'Plataforma Zebrafish Open Doors' Programmementioning

confidence: 99%

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confidence: 99%

Zebrafish Beyond the Bench: The ‘Plataforma Zebrafish Open Doors’ Programme

et al. 2021

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“…In addition to the proven therapeutic effects of Tn P in a preclinical mouse model, analyses of its possible mechanisms of action [ 15 , 16 ], therapeutic index, safety and toxicology [ 17 ] were carried out in the zebrafish model organism.…”

Section: Introductionmentioning

confidence: 99%

The Anti-Inflammatory Peptide TnP Is a Candidate Molecule for Asthma Treatment

Lima

Falcão

Pinto

et al. 2023

Cells

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Asthma is the most common chronic lung disease, with increasing morbidity and mortality worldwide. Accumulation of peribronchial leukocytes is the hallmark of asthma, in particular, eosinophils, which have been reported as the primary cell associated with the induction of airway hyperresponsiveness. Continued exacerbation and accumulation of other leukocytes, such as neutrophils, Th1, and Th17 cells correlate with many of the long-term effects of asthma, such as airway remodeling. We have patented the TnP family of synthetic cyclic peptides, which is in the preclinical phase of developmental studies for chronic inflammatory diseases. The aim of this work was to investigate whether TnP could show anti-inflammatory activity in a murine model of asthma that includes a mixed phenotype of eosinophilic and neutrophilic inflammation. For this, Balb/c mice, sensitized with OVA and exposed to 1% challenge with OVA aerosol, were submitted to prophylactic treatment, receiving TnP at 0.3 mg/kg orally, 1 h before each challenge. We found that sensitized mice challenged with OVA and treated with TnP showed no airway hyperreactivity or lung remodeling. TnP acts systemically in secondary lymphoid organs and locally in the lung, inhibiting the production of Th2/Th17 cytokines. Furthermore, TnP prevented the infiltration of eosinophils and neutrophils in the BAL and lung tissue, inhibited the production of IgE/IgG1, prevented hyperplasia of mucus-producing cells, and decreased the thickening and deposition of sub-epithelial collagen. Our results showed TnP as a candidate molecule for the treatment of airway remodeling associated with inflammatory diseases, such as asthma.

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“…Recent findings showed miRNAs playing a critical role in the regulation of gene expression and in the control of the majority of molecular and cellular pathways throughout eukaryotic organisms and also in viruses ( Singh et al, 2016 ; Al-Ghezi et al, 2019 ). Multiple studies indicate that abnormal expression of miRNAs can control proliferation, apoptosis, maturation, and differentiation of immune cells ( Singh et al, 2016 ; Lv et al, 2018 ; Al-Ghezi et al, 2019 ), as well as they represent a component of the innate immune responses that can restrain inflammatory signaling and interfere in different aspects of inflammation ( Liu et al, 2018 ; Lv et al, 2018 ; Al-Ghezi et al, 2019 ; Disner et al, 2021 ; Pimentel Falcao et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Where the Aryl Hydrocarbon Receptor Meets the microRNAs: Literature Review of the Last 10 Years

Disner

Lopes-Ferreira

Lima

2021

Front. Mol. Biosci.

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The aryl hydrocarbon receptor (AhR) is an environmentally responsive ligand-activated transcription factor, identified in the ‘70s for its toxic responses to halogenated polycyclic aromatic hydrocarbons, such as dioxin. Recently, AhR has been recognized as engaged in multiple physiological processes in health and diseases, particularly in the immune system, inflammatory response, tumorigenesis, and cellular differentiation by epigenetic mechanisms involving miRNAs. However, there is still scarce information about AhR-dependent miRNA regulation and miRNA-mediated epigenetic control in pathologies and therapies. In this review, we explore the mutual regulation of AhR and miRNA over the last decade of studies since many miRNAs have dioxin response elements (DRE) in their 3’ UTR, as well as AhR might contain binding sites of miRNAs. TCDD is the most used ligand to investigate the impact of AhR activation, and the immune system is one of the most sensitive of its targets. An association between TCDD-activated AhR and epigenetic mechanisms like post-transcriptional regulation by miRNAs, DNA methylation, or histone modification has already been confirmed. Besides, several studies have shown that AhR-induced miR-212/132 cluster suppresses cancers, attenuates autoimmune diseases, and has an anti-inflammatory role in different immune responses by regulating cytokine levels and immune cells. Together the ever-expanding new AhR roles and the miRNA therapeutics are a prominent segment among biopharmaceuticals. Additionally, AhR-activated miRNAs can serve as valuable biomarkers of diseases, notably cancer progression or suppression and chemical exposure. Once AhR-dependent gene expression may hinge on the ligand, cell type, and context singularity, the reviewed outcomes might help contextualize state of the art and support new trends and emerging opportunities in the field.

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Knockdown of miR-26a in zebrafish leads to impairment of the anti-inflammatory function of TnP in the control of neutrophilia

Cited by 8 publications

References 39 publications

Zebrafish Beyond the Bench: The ‘Plataforma Zebrafish Open Doors’ Programme

Zebrafish Beyond the Bench: The ‘Plataforma Zebrafish Open Doors’ Programme

The Anti-Inflammatory Peptide TnP Is a Candidate Molecule for Asthma Treatment

Where the Aryl Hydrocarbon Receptor Meets the microRNAs: Literature Review of the Last 10 Years

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