Disruption of immune responses hindered cardiac repair in zebrafish
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE41618 | GEO | 2013/06/24
SECONDARY ACCESSION(S): PRJNA177724
REPOSITORIES: GEO
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Project description:We investigated the role and programming of early immune responses during zebrafish heart regeneration. We found zebrafish treated with anti-inflammatory steroid, beclomethasone, would suffer significantly reduction of its heart regenerative ability, leading to excessive collagen deposition in wound. Microarray approach was used to evaluate the differential expression of heart transcriptome between normal and impaired healing zebrafish, which provides an overall assessment of significant genes that were important for triggering regeneration in the hemostasis-inflammation phase. Three sets of samples each containing 10 zebrafish hearts were used: sham operation, DMSO-1dpa, beclomethasone-1dpa. (dpa= days post amputation) Objects were pre-exposed to water containing 0.25M-NM-<M beclomethasone or DMSO for 1 day. After ventricular resection surgery, objects were sacrificed with their ventricles harvested at the next day (i.e. 1dpa)
2013-06-24 | E-GEOD-41618 | biostudies-arrayexpress
Project description:Myocardial damage caused for example by cardiac ischemia leads to ventricular volume overload resulting in increased stretch of the remaining myocardium. In adult mammals, these changes trigger an adaptive cardiomyocyte hypertrophic response which, if the damage is extensive, will ultimately lead to pathological hypertrophy and heart failure. Conversely, in response to extensive myocardial damage, cardiomyocytes in the adult zebrafish heart and neonatal mice proliferate and completely regenerate the damaged myocardium. We therefore hypothesized that in adult zebrafish, changes in mechanical loading due to myocardial damage may act as a trigger to induce cardiac regeneration. Based, on this notion we sought to identify mechanosensors which could be involved in detecting changes in mechanical loading and triggering regeneration. Here we show using a combination of knockout animals, RNAseq and in vitro assays that the mechanosensitive ion channel Trpc6a is required by cardiomyocytes for successful cardiac regeneration in adult zebrafish. Furthermore, using a cyclic cell stretch assay, we have determined that Trpc6a induces the expression of components of the AP1 transcription complex in response to mechanical stretch. Our data highlights how changes in mechanical forces due to myocardial damage can be detected by mechanosensors which in turn can trigger cardiac regeneration.
2023-12-20 | E-MTAB-13603 | biostudies-arrayexpress
Project description:In the present study, we have used the zebrafish to investigate the anti-inflammatory effects of glucocorticoids. An inflammatory response was induced by amputation of the tail fin of 3dpf zebrafish larvae, and the effect of treatment with the glucocorticoid beclomethasone was investigated. A microarray study was performed to study transcriptional changes 4 hours after amputation and the beclomethasone-induced effects on these changes. Our results show that beclomethasone attenuates almost the entire transcriptional response to amputation. Interestingly, the amputation-induced expression of genes involved in leukotriene biosynthesis appears to be resistant to beclomethasone treatment.
2015-12-01 | GSE69444 | GEO
Project description:Haemophilus influenzae responds to the steroid beclomethasone used in asthma therapy by modulation of biofilm formation and antibiotic tolerance
2019-06-30 | GSE125415 | GEO
Project description:Zebrafish caudal fin regeneration is an established model to study tissue regeneration. In order to identify novel molecular signaling pathways critical for regeneration, we developed a rapid throughput in vivo regeneration assay. We screened a 2000 member structurally diverse small molecule library, followed by assessment of regenerative progression at three days post amputation. A cluster of glucocorticoids was identified among the âpositive hitsâ. To identify the molecular targets of the activated glucocorticoid receptor, microarray analysis was performed using RNA isolated from the regenerates of control and glucocorticoid exposed zebrafish. We identified 673 transcripts that were differentially regulated. The level of expression and spatial expression pattern of select genes were completed by qPCR and by in situ hybridization, respectively. Altogether, these studies demonstrate the power of chemical genetics to identify chemical probes and their targets which will provide a path towards defining conserved regenerative pathways. Experiment Overall Design: The caudal fin of zebrafish larvae at 2days post fertilization were amputated and exposed to vehicle control alone or Beclomethasone . Regenerating fins were isolated at 1days post amputation. Three replicates were collected at each time point. 150 fins were pooled to comprise one replicate.
2009-02-08 | E-GEOD-10766 | biostudies-arrayexpress
Project description:For a short period of time in mammalian neonates, the mammalian heart can regenerate via cardiomyocyte proliferation. This regenerative capacity is largely absent in adults. In other organisms, including zebrafish, damaged hearts can regenerate throughout their lifespans. Many studies have been performed to understand the mechanisms of cardiomyocyte de-differentiation and proliferation during heart regeneration however, the underlying reason why adult zebrafish and young mammalian cardiomyocytes are primed to enter cell cycle have not been identified. Here we show the primed state of a pro-regenerative cardiomyocyte is dictated by its amino acid profile and metabolic state. Adult zebrafish cardiomyocyte regeneration is a result of amino acid-primed mTOR activation. Zebrafish and neonatal mouse cardiomyocytes display elevated glutamine levels, predisposing them to amino acid-driven activation of mTORC1. Injury initiates Wnt/β-catenin signalling that instigates primed mTORC1 activation, Lin28 expression and metabolic remodeling necessary for zebrafish cardiomyocyte regeneration. These studies reveal a unique mTORC1 primed state in zebrafish and mammalian regeneration competent cardiomyocytes.
2022-02-15 | PXD011791 | Pride
Project description:Ischemic cardiopathy is the leading cause of death in the world, for which efficient regenerative therapy is not currently available. In mammals, after a myocardial infarction episode, the damaged myocardium is replaced by scar tissue featuring collagen deposition and tissue remodelling with negligible cardiomyocyte proliferation. Zebrafish, in contrast, display an extensive regenerative capacity as they are able to restore completely lost cardiac tissue after partial ventricular amputation. Due to the lack of genetic lineage tracing evidence, it is not yet clear if new cardiomyocytes arise from existing contractile cells or from an uncharacterised set of progenitors cells. Nonetheless, several genes and molecules have been shown to participate in this process, some of them being cardiomyocyte mitogens in vitro. Though questions as what are the early signals that drive the regenerative response and what is the relative role of each cardiac cell in this process still need to be answered, the zebrafish is emerging as a very valuable tool to understand heart regeneration and devise strategies that may be of potential value to treat human cardiac disease. Here, we performed a genome-wide transcriptome profile analysis focusing on the early time points of zebrafish heart regeneration and compared our results with those of previously published data. Our analyses confirmed the differential expression of several transcripts, and identified additional genes the expression of which is differentially regulated during zebrafish heart regeneration. We validated the microarray data by conventional and/or quantitative RT-PCR. For a subset of these genes, their expression pattern was analyzed by in situ hybridization and shown to be upregulated in the regenerating area of the heart. The specific role of these new transcripts during zebrafish heart regeneration was further investigated ex vivo using primary cultures of zebrafish cardiomyocytes and/or epicardial cells. Our results offer new insights into the biology of heart regeneration in the zebrafish and, together with future experiments in mammals, may be of potential interest for clinical applications. In order to study zebrafish heart regeneration, a time course experiment was realized where amputated heart regenerating were compared to control heart. Samples in triplicate were extracted at 1, 3, 5 and 7 days post-amputation.
2010-03-09 | E-GEOD-17993 | biostudies-arrayexpress
Project description:To uncover the genes regulated by pharmacological activation of the Glucocorticoid Receptor, we performed microarray-based expression profiling of whole zebrafish embryos at 24 and 72 hours post fertilization (hpf) after 3-hour treatment with 25 M-BM-5M of Beclomethasone, a potent glucocorticoid previously tested in zebrafish or with 0.1 % DMSO as control. Embryos at 24 and 72 hpf stages were treated with either 0.1 % DMSO or 25 M-BM-5M Beclomethasone for 3 hours in triplicate experiments and then frozen for RNA extraction.
2012-10-30 | E-GEOD-41904 | biostudies-arrayexpress