Notch2 deficiency prevents muscle atrophy induced by mechanical unloading and diabetes.
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE161693 | GEO | 2022/01/07
REPOSITORIES: GEO
Similar Datasets
Project description:Notch2 deficiency prevents muscle atrophy induced by mechanical unloading and diabetes.
| PRJNA679176 | ENA
Project description:Notch receptors play crucial roles in the cell-fate decisions of tissue stem cells during development and regeneration. Notch1-3 receptors are expressed by satellite cells and their progeny. Here we found that Notch2, but not Notch1 or Notch3, was expressed in fully differentiated myofibers. Using transgenic mice that expressed a muscle-specific active form of Notch2 (N2ICD-mTG), we found that Notch2 activation remarkably reduced muscle mass and strength with a shift toward slow fibers. Transcriptome analyses revealed that growth differentiation factor 11 (GDF11) was highly up-regulated in muscles of N2ICD-mTG mice, and crucially, N2ICD-induced muscle atrophy was rescued by siRNA-mediated reduction of GDF11 expression. These data suggest that Notch2 functions in muscle to regulate muscle mass, in part, through induction of GDF11 expression, and reveal a novel aspect of Notch signaling in a terminally differentiated adult tissue.
2020-01-01 | GSE83929 | GEO
Project description:To investigate the molecular mechanisms governing the transition of skeletal muscle from atrophy to compensatory regeneration and hypertrophy, we employed a mouse model involving hindlimb unloading and subsequent reloading, conducting a comprehensive analysis of global gene expression using RNA-sequencing (RNA-seq). Gastrocnemius muscle samples were obtained from three groups: control mice, mice subjected to 10 days of hindlimb unloading-induced muscle atrophy, and mice reintroduced to normal cage activity for 1 day following the unloading period (reloading).
2023-07-16 | GSE237099 | GEO
Project description:Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure and in ageing. In fact, excessive proteolysis causes cachexia, accelerates disease progression and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, while the transcriptional control of the atrophy-related genes peaks at 3 days, the changes of miRNA expression maximised at 7 days after denervation. Among the different miRNAs, microRNA-206 and 21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified the transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for the fine-tuning of the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions. To determine which miRNAs are relevant for the atrophic process, we performed miRNA expression profiles of muscles from different atrophic models (starvation, denervation and streptozotocin-induced diabetes). We checked whether there was a common signature of miRNA expression in different atrophying conditions and we found that every catabolic situation require a peculiar pattern of miRNA. We further focus on the condition of denervation and identified the most up-regulated miRNAs in this condition, miRNA-206 and miRNA-21.
2014-07-15 | E-GEOD-51648 | biostudies-arrayexpress
Project description:Disuse-induced muscle atrophy is a common clinical problem observed mainly in older adults, intensive care units patients, or astronauts. Previous studies presented biological sex divergence in progression of disuse-induced atrophy along with differential changes in molecular mechanisms possibly underlying muscle atrophy. The aim of this study was to perform transcriptomic profiling of male and female mice during the onset and progression of unloading disuse-induced atrophy. Male and female mice underwent hindlimb unloading (HU) for 24, 48, 72 and 168h (n=8/group). Muscles were weighed for each cohort and gastrocnemius was used for RNA-sequencing analysis. Females exhibited muscle loss as early as 24h of HU, while males after 168h of HU. In males, pathways related to proteasome degradation were upregulated throughout 168-h HU, while in females these pathways were upregulated up to 72-h HU. Lcn2, a gene contributing to regulation of myogenesis, was upregulated by 6.46–19.86-fold across all time points in females only. A reverse expression of Fosb, a gene related to muscle degeneration, was observed between males (4.27-fold up) and females (4.57-fold down) at 24-h HU. Mitochondrial pathways related to TCA cycle were highly downregulated at 168h of HU in males, while in females this downregulation was less pronounced. Collagen-related pathways were consistently downregulated throughout 168-h HU only in females, suggesting a potential biological sex-specific protective mechanism against disuse-induced fibrosis. In conclusion, females may have protection against HU-induced skeletal muscle mitochondrial degeneration and fibrosis through transcriptional mechanisms, although they may be more vulnerable to HU-induced muscle wasting compared to males.
2023-09-21 | GSE240814 | GEO
Project description:To identify atrophy genes directly targeted by Bcl-3 transactivator at a genome wide level, we performed whole transcript expression array and ChIP-seq for muscles from weight bearing or 5-day hind limb unloaded mice. Genes that showed increased expression with unloading and a Bcl-3 peak in the promoter (from ChIP-seq data) were considered as Bcl-3 direct targets during disuse atrophy. Using ChIP array, we identified 241 direct targets for Bcl-3. Our data describe Bcl-3 as a global regulator both of the proteolysis and the change in energy metabolism that are essential components of muscle atrophy due to disuse. Disuse skeletal muscle atrophy was induced by hind limb unloading. Weight bearing (WB) or 5-day hind limb unloaded (HU) muscles were harvested for total RNA isolation and processed for whole transcript expression profiling. We chose to examine gene expression and Bcl-3 binding from 5-day unloaded muscles because our previous time course study of disuse atrophy suggested that most genes are differentially regulated at this time point, and thus, would best represent the time for Bcl-3 binding to the gene targets of the NF-kB transcriptional network.
2012-11-10 | E-GEOD-40578 | biostudies-arrayexpress
Project description:Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure and in ageing. In fact, excessive proteolysis causes cachexia, accelerates disease progression and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, while the transcriptional control of the atrophy-related genes peaks at 3 days, the changes of miRNA expression maximised at 7 days after denervation. Among the different miRNAs, microRNA-206 and 21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified the transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for the fine-tuning of the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions.
2014-07-15 | GSE51648 | GEO
Project description:Loss of muscle proteins and the consequent weakness has important clinical consequences in diseases such as cancer, diabetes, chronic heart failure and in ageing. In fact, excessive proteolysis causes cachexia, accelerates disease progression and worsens life expectancy. Muscle atrophy involves a common pattern of transcriptional changes in a small subset of genes named atrophy-related genes or atrogenes. Whether microRNAs play a role in the atrophy program and muscle loss is debated. To understand the involvement of miRNAs in atrophy we performed miRNA expression profiling of mouse muscles under wasting conditions such as fasting, denervation, diabetes and cancer cachexia. We found that the miRNA signature is peculiar of each catabolic condition. We then focused on denervation and we revealed that changes in transcripts and microRNAs expression did not occur simultaneously but were shifted. Indeed, while the transcriptional control of the atrophy-related genes peaks at 3 days, the changes of miRNA expression maximised at 7 days after denervation. Among the different miRNAs, microRNA-206 and 21 were the most induced in denervated muscles. We characterized their pattern of expression and defined their role in muscle homeostasis. Indeed, in vivo gain and loss of function experiments revealed that miRNA-206 and miRNA-21 were sufficient and required for atrophy program. In silico and in vivo approaches identified the transcription factor YY1 and the translational initiator factor eIF4E3 as downstream targets of these miRNAs. Thus miRNAs are important for the fine-tuning of the atrophy program and their modulation can be a novel potential therapeutic approach to counteract muscle loss and weakness in catabolic conditions.
2014-07-15 | GSE52676 | GEO
Project description:Muscle atrophy is associated with aging (sarcopenia) and chronic unloading (such as bed confinement and immobilization with casts), as well as various pathological conditions such as type 1 diabetes and nerve injury (denervation). The hindlimb skeletal muscles of C57BL/6 mice (9 weeks old, male) were immobilized (unloaded) by a plaster cast. After 11 days, skeletal muscle was collected and RNA extracted. Expression of Dnmt3a was reduced while expression of Gdf5 was increased by plaster cast immobilization compared to age-matched control mice.
2019-04-01 | GSE97312 | GEO
Project description:Microgravity and prolonged periods of inactivity cause a variety of diseases, including skeletal muscle mass loss and weakening as well as cardiovascular deconditioning. The primary causes of the inadequate preventative measures for these deconditionings are the lack of biomarkers and unknown underlying mechanisms of cardiovascular and skeletal muscle deconditioning in these conditions. Here, we used a hindlimb unloading (HU) mouse model that replicates astronauts in space and bedridden patients to first evaluate cardiovascular and skeletal muscle performance. Serum samples from these mice were used to identify new biomarkers using metabolomic and proteomic approaches. Three weeks of unloading resulted in alterations in cardiovascular system function in C57/Bl6 mice, as measured by changes in mean arterial pressure and heart weight. Unloading for three weeks also altered skeletal muscle function, resulting in a decrease of grip strength in HU mice, as well as skeletal muscle atrophy, as shown by a drop in muscle mass. A two-week recovery time from the unloading condition partially reversed these alterations, stressing the importance of the recovery process.
2024-01-26 | PXD042753 | Pride