Distinct macrophage phenotypes and redox environment during the fin fold regenerative process in zebrafish

Paredes, Laís Cavalieri; Luz, Rebeca Bosso dos Santos; Tozzi, Ollavo Nogueira; Carvalho, Lucicleide; Calado, Sabrina Loise de Morais; Padovani, Bárbara Nunes; Fénero, Camila Idelí Morales; Amaral, Mariana Abrantes do; Assis, Helena Cristina da Silva de; Câmara, Niels Olsen Saraiva; Braga, Tárcio Teodoro

doi:10.1111/sji.13026

Cited by 6 publications

(5 citation statements)

References 69 publications

(129 reference statements)

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“…Oxidative stress and inflammation are well known to be key factors initiating regenerative processes in mammals and zebrafish ( Schäfer and Werner, 2008 ; Koh and DiPietro, 2011 ; Dunnill et al, 2017 ; Nguyen-Chi et al, 2017 ; Paredes et al, 2021 ). Since caudal fin amputation in zebrafish has become a valuable model for better understanding tissue regenerative processes ( Lebedeva et al, 2020 ), we decided to use this model to monitor the potential regenerative properties of H. lanceolatum .…”

Section: Resultsmentioning

confidence: 99%

“…Our results revealed the preventive antioxidant capacity of H. lanceolatum extract after tail amputation, but the therapeutic treatment was inefficient. This difference may be explained by the activation of the antioxidant defenses including antioxidant enzymes throughout H. lanceolatum pretreatment, prior to injury ( Paredes et al, 2021 ). In parallel, we monitored the recruitment of macrophages and neutrophils at the site of injury 6 h after the tail sectioning.…”

Section: Discussionmentioning

confidence: 99%

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Hypericum lanceolatum Lam. Medicinal Plant: Potential Toxicity and Therapeutic Effects Based on a Zebrafish Model

et al. 2022

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Hypericum lanceolatum Lam. (H. lanceolatum) is a traditional medicinal plant from Reunion Island used for its pleiotropic effects mainly related to its antioxidant activity. The present work aimed to 1) determine the potential toxicity of the plant aqueous extract in vivo and 2) investigate its putative biological properties using several zebrafish models of oxidative stress, regeneration, estrogenicity, neurogenesis and metabolic disorders. First, we characterized the polyphenolic composition by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and identified chlorogenic acid isomers, quercetin and kaempferol derivatives as the major compounds. We then evaluated for the first time the toxicity of an aqueous extract of H. lanceolatum and determined a maximum non-toxic concentration (MNTC) in zebrafish eleutheroembryos from 0 to 96 hpf following OECD (Organization for Economic Cooperation and Development) guidelines. This MNTC test was also determined on hatched eleutheroembryos after 2 days of treatment (from 3 to 5 dpf). In our study, the anti-estrogenic effects of H. lanceolatum are supported by the data from the EASZY assay. In a tail amputation model, we showed that H. lanceolatum at its MNTC displays antioxidant properties, favors immune cell recruitment and tissue regeneration. Our results also highlighted its beneficial effects in metabolic disorders. Indeed, H. lanceolatum efficiently reduces lipid accumulation and body mass index in overfed larva- and adult-models, respectively. In addition, we show that H. lanceolatum did not improve fasting blood glucose levels in a hyperglycemic zebrafish model but surprisingly inhibited neurogenesis impairment observed in diabetic conditions. In conclusion, our study highlights the antioxidant, pro-regenerative, anti-lipid accumulation and pro-neurogenic effects of H. lanceolatum in vivo and supports the use of this traditional medicinal plant as a potential alternative in the prevention and/or treatment of metabolic disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hypericum lanceolatum Lam. Medicinal Plant: Potential Toxicity and Therapeutic Effects Based on a Zebrafish Model

et al. 2022

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“…Considering the role of antioxidant response during larval fish fin amputation [ 20 ] and since the Nrf2/ARE pathway has been shown to play a key role during diabetic wound regeneration [ 21 ], we tested whether fin amputation in Tg(8XAORE:EGFP) ia201 larvae could affect reporter expression. Toward this aim, we performed fin amputation in 3 dpf and 6 dpf transgenic larvae and monitored reporter activity changes by confocal microscopy.…”

Section: Resultsmentioning

confidence: 99%

Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System

Badenetti

Manzoli

Rubin

et al. 2023

IJMS

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Among multiple cytoprotective mechanisms, eukaryotic cells exhibit a complex transcriptional program relying on the Nrf2 transcription factor, which is generally recruited upon biological stressors including oxidative-stress-based cellular insults. The relevance of this master regulator has remarkably emerged in recent years in several research fields such as cancer, inflammatory disorders and age-related neurological diseases. Here, we document the generation and characterization of a novel Nrf2/ARE pathway biosensor fish which exhibits a dynamic spatiotemporal expression profile during the early developmental stages. The transgenic line is responsive to known Nrf2 pathway modulators but also to Edaravone, which direct activity on the Nrf2 pathway has never been documented in a live transgenic fish model. We also show that the reporter is faithfully activated during fin regeneration, and its degree of expression is slightly affected in a glucocerebrosidase (Gba1) morphant zebrafish model. Therefore, this novel transgenic fish may represent a valuable tool to be exploited for the characterization of zebrafish models of human diseases, as well as for primary high-throughput drug screening.

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“…Moreover, the zebrafish possesses an adaptive immune system comprising of T cells and B cells (25)(26)(27)(28)(29)(30), which makes this model useful to study the role of adaptive immune cells during appendages regeneration. Although innate immune cells have been investigated in the zebrafish fin regeneration (31)(32)(33)(34)(35), the functional role of adaptive immune cells in epimorphic fin regeneration remains unclear. Using a transgenic cell ablation model and genetic mutants, here we have identified a novel role of Tregs in caudal fin regeneration, whereby Tregs promote blastemal cell proliferation by producing Igf2a and Igf2b in a finspecific manner.…”

Section: Introductionmentioning

confidence: 99%

Regulatory T cells regulate blastemal proliferation during zebrafish caudal fin regeneration

et al. 2022

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The role of T cells in appendage regeneration remains unclear. In this study, we revealed an important role for regulatory T cells (Tregs), a subset of T cells that regulate tolerance and tissue repair, in the epimorphic regeneration of zebrafish caudal fin tissue. Upon amputation, fin tissue-resident Tregs infiltrate into the blastema, a population of progenitor cells that produce new fin tissues. Conditional genetic ablation of Tregs attenuates blastemal cell proliferation during fin regeneration. Blastema-infiltrating Tregs upregulate the expression of igf2a and igf2b, and pharmacological activation of IGF signaling restores blastemal proliferation in Treg-ablated zebrafish. These findings further extend our understandings of Treg function in tissue regeneration and repair.

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Distinct macrophage phenotypes and redox environment during the fin fold regenerative process in zebrafish

Cited by 6 publications

References 69 publications

Hypericum lanceolatum Lam. Medicinal Plant: Potential Toxicity and Therapeutic Effects Based on a Zebrafish Model

Hypericum lanceolatum Lam. Medicinal Plant: Potential Toxicity and Therapeutic Effects Based on a Zebrafish Model

Monitoring Nrf2/ARE Pathway Activity with a New Zebrafish Reporter System

Regulatory T cells regulate blastemal proliferation during zebrafish caudal fin regeneration

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