Transcriptional reprogramming during reloading of atrophied rat soleus muscle
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE4492 | GEO | 2006/03/17
SECONDARY ACCESSION(S): PRJNA94371
REPOSITORIES: GEO
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Project description:This SuperSeries is composed of the following subset Series: GSE667: C14 GSE668: HS14 GSE669: HS-R1 GSE1084: HS-R5 Refer to individual Series
2006-03-16 | E-GEOD-4492 | biostudies-arrayexpress
Project description:Aged skeletal muscle is characterized by poor muscle recovery following disuse coinciding with an impaired muscle pro-inflammatory macrophage response. Macrophage inflammatory status is regulated by its metabolic state, but little is understood of macrophage metabolism and its relation to macrophage inflammation in the context of muscle recovery and aging. Therefore, the purpose of this study was to thoroughly characterize macrophage metabolism and inflammation in aged muscle during early recovery following disuse atrophy using single cell transcriptomics and functional assays. Young (4-5 months) and old (20-22 months) male C57BL/6 mice underwent 14 days of hindlimb unloading followed by 4 days of ambulatory recovery. CD45+ cells were isolated from solei muscles and analyzed using 10x Genomics single cell RNA sequencing. We found that aged pro-inflammatory macrophage clusters were characterized with an impaired inflammatory and glycolytic transcriptome, and this dysregulation was accompanied by a suppression of HIF-1α and its immediate downstream target, Glut1. As a follow-up, bone marrow-derived macrophages were isolated from a separate cohort of young and old mice at 4-d recovery and were polarized to a pro-inflammatory phenotype and used for glycolysis stress test, phagocytosis activity assay, and targeted GC-MS metabolomics. Aged bone marrow-derived pro-inflammatory macrophages were characterized with impaired glycolysis and phagocytosis function, decreased succinate and an accumulation of glycolytic metabolic intermediates overall supporting reduced glycolytic flux and macrophage function. Our results indicate that the metabolic reprograming and function of aged skeletal muscle pro-inflammatory macrophages are dysfunctional during early recovery from disuse atrophy possibly attributing to attenuated regrowth.
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2019-04-01 | GSE97315 | GEO
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2009-12-31 | GSE16466 | GEO
Project description:Massage is a viable mechanotherapy to improve protein turnover during disuse atrophy and improve muscle regrowth during recovery from disuse atrophy in adult muscle. Therefore, we investigated whether massage can cause beneficial adaptations in skeletal muscle from aged rats during normal weight-bearing (WB) conditions, hindlimb suspension (HS), or reloading (RE) following HS. Aged (30 months) male Fischer 344/Brown Norway rats were divided into two experiments: (1) WB for 7 days (WB, n = 8), WB with massage (WBM, n = 8), HS for 7 days (HS7, n = 8), or HS with massage (HSM, n = 8), and (2) WB for 14 days (WB14, n = 8), HS for 14 days (HS14, n = 8), reloading (RE, n = 10), or reloading with massage (REM, n = 10) for 7 days following HS. Deuterium oxide (D2O) labeling was used to assess dynamic protein and ribosome turnover in each group and anabolic signaling pathways were assessed. Massage did have an anabolic benefit during RE or WB. In contrast, massage during HS enhanced myofibrillar protein turnover in both the massaged limb and contralateral non-massaged limb compared with HS, but this did not prevent muscle loss. Overall, the data demonstrate that massage is not an effective mechanotherapy for prevention of atrophy during muscle disuse or recovery of muscle mass during reloading in aged rats.
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Project description:The myosin heavy chain (MHC) isoform composition of skeletal muscle is dependent, in part, on the functional demands of the muscle. The rat soleus muscle primarily expresses the slow-contracting type I MHC; however, chronic inactivity increases expression of the faster-contracting type II MHC isoforms. The purpose of this study was to identify the type IIb MHC promoter region(s) that regulate de novo transcription during chronic inactivity of the soleus induced by spinal cord isolation (SI; complete mid-thoracic and high sacral spinal cord transections plus deafferentation). Seven days after SI, transcription of IIb MHC was evidenced by increases in IIb pre-mRNA and mRNA. The activity of an approximately 2.2-kb IIb promoter-firefly luciferase reporter plasmid increased in SI soleus over control as compared to that of a promoterless plasmid. Deletion analyses indicated that the regions encompassing -2237 to -1431, -1048 to -461, and -192 to -161 basepairs (bp) each contributed to the increase in transcriptional activity. Moreover, deletions or mutations of AT-rich regions in the proximal -192 bp region abolished the increased promoter activity. These results provide important insights related to how proximal IIb MHC promoter elements regulate the increased expression of the IIb MHC gene in response to inactivity of a predominantly slow postural muscle as it undergoes a remodeling of its phenotype and functional characteristics.
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2023-09-06 | GSE217577 | GEO
Project description:Amongst reduced gravity simulators, the lower body positive pressure (LBPP) treadmill is emerging as an innovative tool for both rehabilitation and fundamental research purposes as it allows running while experiencing reduced vertical ground reaction forces. The appropriate use of such a treadmill requires an improved understanding of the associated neuromechanical changes. This study concentrates on the runner's adjustments to LBPP-induced unweighting and reloading during running. Nine healthy males performed two running series of nine minutes at natural speed. Each series comprised three sequences of three minutes at: 100% bodyweight (BW), 60 or 80% BW, and 100% BW. The progressive unweighting and reloading transitions lasted 10 to 15 s. The LBPP-induced unweighting level, vertical ground reaction force and center of mass accelerations were analyzed together with surface electromyographic activity from 6 major lower limb muscles. The analyses of stride-to-stride adjustments during each transition established highly linear relationships between the LBPP-induced progressive changes of BW and most mechanical parameters. However, the impact peak force and the loading rate systematically presented an initial 10% increase with unweighting which could result from a passive mechanism of leg retraction. Another major insight lies in the distinct neural adjustments found amongst the recorded lower-limb muscles during the pre- and post-contact phases. The preactivation phase was characterized by an overall EMG stability, the braking phase by decreased quadriceps and soleus muscle activities, and the push-off phase by decreased activities of the shank muscles. These neural changes were mirrored during reloading. These neural adjustments can be attributed in part to the lack of visual cues on the foot touchdown. These findings highlight both the rapidity and the complexity of the neuromechanical changes associated with LBPP-induced unweighting and reloading during running. This in turn emphasizes the need for further investigation of the evolution over time of these neuromechanical changes.
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Project description:The structure and function of soleus muscle fibers undergo substantial remodeling under real or simulated microgravity conditions. However, unloading-induced changes in the functional activity of skeletal muscle primary myoblasts remain poorly studied. The purpose of our study was to investigate how short-term and long-term mechanical unloading would affect cultured myoblasts derived from rat soleus muscle. Mechanical unloading was simulated by rat hindlimb suspension model (HS). Myoblasts were purified from rat soleus at basal conditions and after 1, 3, 7, and 14 days of HS. Myoblasts were expanded in vitro, and the myogenic nature was confirmed by their ability to differentiate as well as by immunostaining/mRNA expression of myogenic markers. The proliferation activity at different time points after HS was analyzed, and transcriptome analysis was performed. We have shown that soleus-derived myoblasts differently respond to an early and later stage of HS. At the early stage of HS, the proliferative activity of myoblasts was slightly decreased, and processes related to myogenesis activation were downregulated. At the later stage of HS, we observed a decrease in myoblast proliferative potential and spontaneous upregulation of the pro-myogenic program.
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