Similar Datasets
Project description:Effect of glucocorticoid receptor deletion on gene expression of cardiomyocytes at neonatal and early postnatal stages
| PRJNA838129 | ENA
Project description:Previous studies show that androgens are involved in hypertrophy and excitability of cardiomyocytes and that their effects are mediated through their receptor. The aim of this study was to evaluate the presence of androgen receptor (AR) in mouse heart during prenatal and early postnatal stages.The expression of AR and related genes, alpha myosin heavy chain -Myh6-, beta myosin heavy chain -Myh7- and atrial natriuretic factor -Nppa- was simultaneously evaluated by semiquantitative RT-PCR. AR was also detected by immunohistochemistry. Androgen receptor mRNA was detected in hearts from 10.5 days post coitum to 16 postnatal days. A higher expression of AR mRNA in atria compared to ventricles was observed in neonatal mouse. A positive correlation between mRNA levels of AR and Nppa was observed in mouse heart at early postnatal development. Androgen receptor expression is similar in males and females during cardiac development. Finally, androgen receptor protein was observed by immunohistochemistry in myocardial cells of atria and ventricles from 12.5 days onwards and restricted after 16.5 days post-coitum to nuclei of cardiomyocytes.Present results provide evidence that androgen receptor is expressed from prenatal stages in mouse heart, supporting the proposition that androgens could be involved in mammalian heart development.
| S-EPMC5557468 | biostudies-literature
Project description:To investigate the role of the glucocorticoid receptor (GR) in the regulation of cardiomyocyte maturation and proliferation, we established a cardiomyocyte-specific GR knock-out (GR-cKO) mouse model by Cre-Lox technology. We thus performed gene expression profiling analysis using data obtained from RNA-seq of cardiomyocytes isolated from GR-cKO and control mouse models at neonatal stage and cultured in vitro. Our analyses unveiled a role for GR in regulating gene networks related to the energetic metabolism, which in turn may impact on cardiomyocyte proliferative and regenerative ability.
2022-05-16 | GSE202968 | GEO
Project description:To investigate the role of the glucocorticoid receptor (GR) in the regulation of cardiomyocyte maturation and proliferation, we established a cardiomyocyte-specific GR knock-out (GR-cKO) mouse model by Cre-Lox technology. We thus performed gene expression profiling analysis using data obtained from RNA-seq of the cardiac tissue of GR-cKO and control mouse models extracted during the early postnatal development. Our analyses unveiled a role for GR in regulating gene networks related to the energetic metabolism, which in turn may impact on cardiomyocyte proliferative and regenerative ability.
2022-05-16 | GSE202969 | GEO
Project description:Effect of cardiomyocyte-specific deletion of glucocorticoid receptor on gene expression of cultured neonatal cardiomyocytes
| PRJNA837897 | ENA
Project description:Background An increase in serum cortisol has been identified as a risk factor for cardiac failure, which highlights the impact of glucocorticoid signaling in cardiomyocytes and its influence in the progression of failure. Dexamethasone, a synthetic glucocorticoid, is sufficient for induction of cardiomyocyte hypertrophy, but little is known of the glucocorticoid receptor (GR) genome-binding and -dependent transcriptional changes that mediate this phenotype. Methods and Results In this study using high-resolution sequencing, we identified genomic targets of GR and associated change in the transcriptome after 1 and 24 hours of dexamethasone treatment. We showed that GR associates with 6482 genes in the cardiac genome, with differential regulation of 738 genes. Interestingly, alignment of the chromatin immunoprecipitation and RNA sequencing data show that, after 1 hour, 69% of differentially regulated genes are associated with GR and identify as regulators of RNA pol II-dependent transcription. Conversely, after 24 hours only 45% of regulated genes are associated with GR and involved in dilated and hypertrophic cardiomyopathies as well as other growth-related pathways. In addition, our data also reveal that a majority of genes (76.42%) associated with GR show incremental changes in transcript abundance and are genes involved in basic cellular processes that might be regulated by the dynamics of promoter-paused RNA pol II, as seen in hearts undergoing hypertrophy. In vivo administration of dexamethasone resulted in similar changes in the cardiac transcriptome, as seen in isolated cardiomyocytes. Conclusions Our data reveal genome-wide GR binding sites in cardiomyocytes, identify novel targets and GR-dependent change in the transcriptome that induces and contributes to cardiomyocyte hypertrophy.
| S-EPMC6475044 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2019-08-20 | GSE114767 | GEO
Project description:FKBP51 (FK506-binding protein 51) is a known co-chaperone and regulator of the glucocorticoid receptor (GR), which usually attenuates its activity. FKBP51 is one of the major GR target genes in skin, but its role in clinical effects of glucocorticoids is not known. Here, we used FKBP51 knockout (KO) mice to determine FKBP51's role in the major adverse effect of topical glucocorticoids, skin atrophy. Unexpectedly, we found that all skin compartments (epidermis, dermis, dermal adipose and CD34+ stem cells) in FKBP51 KO animals were much more resistant to glucocorticoid-induced hypoplasia. Furthermore, despite the absence of inhibitory FKBP51, the basal level of expression and glucocorticoid activation of GR target genes were not increased in FKBP51 KO skin or CRISPR/Cas9-edited FKBP51 KO HaCaT human keratinocytes. FKBP51 is known to negatively regulate Akt and mTOR. We found a significant increase in AktSer473 and mTORSer2448 phosphorylation and downstream pro-growth signaling in FKBP51-deficient keratinocytes in vivo and in vitro. As Akt/mTOR-GR crosstalk is usually negative in skin, our results suggest that Akt/mTOR activation could be responsible for the lack of increased GR function and resistance of FKBP51 KO mice to the steroid-induced skin atrophy.
| S-EPMC6205168 | biostudies-literature
Project description:BACKGROUND: Glucocorticoids have an important role in early growth and development. Glucocorticoid receptor gene polymorphisms have been identified that contribute to the variability in glucocorticoid sensitivity. We examined whether these glucocorticoid receptor gene polymorphisms are associated with growth in fetal and early postnatal life. METHODS: This study was embedded in a population-based prospective cohort study from fetal life onwards. The studied glucocorticoid receptor gene polymorphisms included BclI (rs41423247), TthIIII (rs10052957), GR-9beta (rs6198), N363S (rs6195) and R23K (rs6789 and6190). Fetal growth was assessed by ultrasounds in second and third trimester of pregnancy. Anthropometric measurements in early childhood were performed at birth and at the ages of 6, 14 and 24 months postnatally. Analyses focused on weight, length and head circumference. Analyses were based on 2,414 healthy, Caucasian children. RESULTS: Glucocorticoid receptor gene polymorphisms were not associated with fetal weight, birth weight and early postnatal weight. Also, no associations were found with length and head circumference. Neither were these polymorphisms associated with the risks of low birth weight or growth acceleration from birth to 24 months of age. CONCLUSIONS: We found in a large population-based cohort no evidence for an effect of known glucocorticoid receptor gene polymorphisms on fetal and early postnatal growth characteristics. Further systematic searches for common genetic variants by means of genome-wide association studies will enable us to obtain a more complete understanding of what genes and polymorphisms are involved in growth in fetal life and infancy.
| S-EPMC2846902 | biostudies-literature
Project description:Inappropriate excess of the steroid hormone aldosterone, which is a mineralocorticoid receptor (MR) agonist, is associated with increased inflammation and risk of cardiovascular disease. MR antagonists are cardioprotective and antiinflammatory in vivo, and evidence suggests that they mediate these effects in part by aldosterone- independent mechanisms. We used affymetrix to characterize the effect of Mineralocorticoid Receptor deletion on macrophage transcriptional profile, and identify its requirement in normal glucocorticoid signalling. We isolated mouse peritoneal macrophages from Myeloid MRKO mice and Floxed Controls, cultured in the presence or absence of corticosterone. RNA was extracted for Affymetrix cDNA hybridization. Each sample was pooled from experiments performed in triplicate.
2010-07-30 | E-GEOD-23308 | biostudies-arrayexpress