Expression data from quadriceps of utrn+/-;mdx mice treated with spironolactone plus lisinopril compared to untreated
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE70984 | GEO | 2015/07/17
SECONDARY ACCESSION(S): PRJNA290075
REPOSITORIES: GEO
Similar Datasets
Project description:To identify the gene expression differences in skeletal muscles resulting from treatment of dystrophic mice with spironolactone plus lisinopril, eplerenone plus lisinopril or prednisolone.
2017-03-07 | GSE84876 | GEO
Project description:To identify the gene expression differences in skeletal muscles resulting from conditional knockout of the mineralocorticoid receptor in myofibers and myeloid cells in dystrophin-deficient mdx mice
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Project description:Fibro-adipogenic progenitors (FAPs) are emerging cellular components of the skeletal muscle regenerative environment. The alternative functional phenotype of FAPs - either supportive of muscle regeneration or promoting fibro-adipogenic degeneration - is a key determinant in the pathogenesis of muscular diseases, including Duchenne Muscular Dystrophy (DMD). However, the molecular regulation of FAPs is still unknown. We show here that an "HDAC-myomiR-BAF60 variant network" regulates the functional phenotype of FAPs in dystrophic muscles of mdx mice. Combinatorial analysis of gene expression microarray and genome-wide chromatin remodeling by Nuclease accessibility (NA)-seq revealed that HDAC inhibitors de-repress a "latent" myogenic program in FAPs from dystrophic muscles at early stages of disease progression. In these cells HDAC inhibition promoted the expression of two core components of the myogenic transcriptional machinery, MyoD and BAF60C, and upregulated the myomiRs (miRs) miR-1.2, miR-133 and miR-206, which target two alternative BAF60 variants (BAF60A and B) ultimately leading to the activation of a pro-myogenic program at the expense of the fibro-adipogenic phenotype. By contrast, FAPs from dystrophic muscles at late stages of disease progression displayed resistance to HDACi-induced chromatin remodeling at myogenic loci and fail to activate the pro-myogenic phenotype. These results reveal a previously unappreciated disease stage-specific bipotency of mesenchimal cells within the regenerative environment of dystrophic muscles. Resolution of such bi-potency by epigenetic interventions, such as HDACi, provides the molecular rationale for the in situ reprogramming of target cells to promote therapeutic regeneration of dystrophic muscles. miRNA modulation upon Histone Deacetylase inhibition in Fibro-Adipogenic Progenitors (FAPs) derived from young mdx mice was evaluated by small RNA-sequencing in 2 controls and 2 treated samples
2014-04-23 | E-GEOD-51933 | biostudies-arrayexpress
Project description:Fibro-adipogenic progenitors (FAPs) are emerging cellular components of the skeletal muscle regenerative environment. The alternative functional phenotype of FAPs - either supportive of muscle regeneration or promoting fibro-adipogenic degeneration - is a key determinant in the pathogenesis of muscular diseases, including Duchenne Muscular Dystrophy (DMD). However, the molecular regulation of FAPs is still unknown. We show here that an "HDAC-myomiR-BAF60 variant network" regulates the functional phenotype of FAPs in dystrophic muscles of mdx mice. Combinatorial analysis of gene expression microarray and genome-wide chromatin remodeling by Nuclease accessibility (NA)-seq revealed that HDAC inhibitors de-repress a "latent" myogenic program in FAPs from dystrophic muscles at early stages of disease progression. In these cells HDAC inhibition promoted the expression of two core components of the myogenic transcriptional machinery, MyoD and BAF60C, and upregulated the myomiRs (miRs) miR-1.2, miR-133 and miR-206, which target two alternative BAF60 variants (BAF60A and B) ultimately leading to the activation of a pro-myogenic program at the expense of the fibro-adipogenic phenotype. By contrast, FAPs from dystrophic muscles at late stages of disease progression displayed resistance to HDACi-induced chromatin remodeling at myogenic loci and fail to activate the pro-myogenic phenotype. These results reveal a previously unappreciated disease stage-specific bipotency of mesenchimal cells within the regenerative environment of dystrophic muscles. Resolution of such bi-potency by epigenetic interventions, such as HDACi, provides the molecular rationale for the in situ reprogramming of target cells to promote therapeutic regeneration of dystrophic muscles.
2014-04-23 | GSE51933 | GEO
Project description:To uncover whether aldosterone induces gene expression changes through mineralocorticoid or glucocorticoid receptors and determine if eplerenone and spironolactone could block aldosterone induced gene expression to the same extent
2017-05-05 | GSE84991 | GEO
Project description:The purpose of this study was to examine the effect of aldosterone receptor blockade on the immunopathogenesis and progression of nephritis in the (NZBxNZW) F1 murine lupus model. Female NZB/W F1 mice (11 weeks old) were treated daily with 25 or 50 mg/kg of oral spironolactone or vehicle. Proteinuria, renal function and serum autoantibody levels were monitored. Renal histopathology, immune complex deposition, and immunohistochemistry were analyzed at various time points. Targeted microarray analysis was performed on renal tissue, with subsequent real time PCR analysis of several differentially expressed genes. At 36 weeks of age, 8 mice from each treatment group (vehicle, 25 mg/kg/d spironolactone and 50 mg/kg/d spironolactone) were anesthetized and perfused with cold saline; then one kidney per mouse was removed , homogenized in Tripure, and frozen at -80 until RNA extraction. RNA was extracted using Tripure and a Qiagen RNEasy Minikit. RNA was pooled equally by weight within each treatment group and frozen at -80. Subsequently, the three batches of pooled RNA were processed for microarray analysis.
2010-05-26 | E-GEOD-10144 | biostudies-arrayexpress
Project description:Effects of Pten knockout in dystrophic skeletal muscles of mdx mouse
| PRJNA631535 | ENA
Project description:In our recent study was shown a significant recovery of damaged skeletal muscle of mice with X-linked muscular dystrophy (mdx) following low-intensity endurance exercise, probably by reducing the degeneration of dystrophic muscle. Consequently, in the present work, we aimed to identify proteins involved in the observed reduction in degenerating fibres. To this end, we used proteomic analysis to evaluate changes in the protein profile of quadriceps dystrophic muscles of exercised compared with sedentary mdx mice. Four protein spots were found to be significantly changed and were identified as three isoforms of carbonic anhydrase 3 (CA3) and superoxide dismutase [Cu-Zn] (SODC). Protein levels of CA3 isoforms were significantly up-regulated in quadriceps of sedentary mdx mice and were completely restored to wild-type (WT) mice values, both sedentary and exercised, in quadriceps of exercised mdx mice. Protein levels of SODC were down-regulated in quadriceps of sedentary mdx mice and were significantly restored to WT mice values, both sedentary and exercised, in quadriceps of exercised mdx mice. Western blot data were in agreement with those obtained using proteomic analysis and revealed the presence of one more CA3 isoform that was significantly changed. Based on data found in the present study, it seems that low-intensity endurance exercise may in part contribute to reduce cell degeneration process in mdx muscles, by counteracting oxidative stress.
| S-EPMC4613691 | biostudies-literature
Project description:To identify the transcriptional regulatory mechanisms associated with the biological anti-edematous and anti-inflammatory effect of spironolactone, we performed an analysis of the regulated genes in the neuroretina of GK rats aged 14 months and treated with a formulation of Spironolacton-loaded Microspheres (Sp-MSs) that released spironolactone for at least 2 months (mean size 30µm, 1µg/mg MSs/day). RNA-sequencing was performed on the neural retina and non-loade microspheres (NL-MSs) served as control treatment. The heatmaps of genes differentially regulated by Sp-MSs individuals as compared to NL-MSs showed a clear difference between the two conditions with 114 genes significantly regulated between the two groups, 27 significantly down regulated and 87 significantly up regulated (Log2FC ≥ 0,5, adjusted p<0.05). Pathway enrichment analysis using hallmark gene-set function highlighted 9 significantly regulated pathways: unfolded protein response, UV response, G2M checkpoint, allograft rejection, interferon gamma response, MTORC1 signaling, oxidative phosphorylation, MYC targets and adipogenesis (Figure EV 3B, C). Genes encoding proteins known to intervene in vascular permeability and retinal edema were counter regulated by Sp-MSs including Vldlr, Sesn2, Adcyap1, Dusp8, Pten, Slc7a1, Tjp1, Dlg1, Sema7a, although Vegf was rather up-regulated, suggested an anti-edematous mechanism independent from VEGF. The effect of Sp-MSs was confirmed by quantitative PCR for number of these genes demonstrating that spironolactone acts as a transcriptional regulator to normalize the diabetic retina.
2021-08-26 | GSE163255 | GEO
Project description:Transcriptome analysis of hindlimb muscles from dystrophic mice. The mdx mouse is a good genetic and molecular murine model for Duchenne Muscular Dystrophy (DMD), a progressive and devastating muscle disease. However, this model is inappropriate for testing new therapies due to its mild phenotype. Here, we transferred the mdx mutation to the 129/Sv strain with the aim to create a more severe model for DMD. Unexpectedly, functional analysis of the first three generations of mdx129 showed a progressive amelioration of the phenotype, associated to less connective tissue replacement, and more regeneration than the original mdxC57BL. Transcriptome comparative analysis was performed to identify what is protecting this new model from the dystrophic characteristics. The mdxC57BL presents three times more differentially expressed genes (DEGs) than the mdx129 (371 and 137 DEGs, respectively). However, both models present more overexpressed genes than underexpressed, indicating that the dystrophic and regenerative alterations are associated with the activation rather than repression of genes. As to functional categories, the DEGs of both mdx models showed a predominance of immune system genes. Excluding this category, the mdx129 model showed a decreased participation of the endo/exocytic pathway and homeostasis categories, and an increased participation of the extracellular matrix and enzymatic activity categories. Spp1 gene overexpression was the most significant DEG exclusively expressed in the mdx129 strain. This was confirmed through relative mRNA analysis and osteopontin protein quantification. The amount of the 66 kDa band of the protein, representing the post-translational product of the gene, was about 4.8 times higher on Western blotting. Spp1 is a known DMD prognostic biomarker, and our data indicate that its upregulation can benefit phenotype. Modeling the expression of the DEGs involved in the mdx mutation with a benign course should be tested as a possible therapeutic target for the dystrophic process. We analyzed calf muscles from five Dmdmdx, three hybrids of Dmdmdx with 129/Sv in generations F1, F2 and F3; five C57BL/6 and three 129/Sv as normal controls. All animals were six months old. We used the Affymetrix Mouse Gene 1.0 ST platform. Array data was processed by Expression Console. No technical replicates were performed.
2016-07-24 | E-GEOD-77126 | biostudies-arrayexpress