Ontology highlight
ABSTRACT:
PROVIDER: PRJNA905121 | ENA |
REPOSITORIES: ENA
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Project description:Understanding the way in which the airway heals in response to injury is fundamental to dissecting the mechanisms underlying airway disease pathology. Only limited data is available in relation to in vivo characterisation of the molecular features of repair in the airway. This study sought to characterise the dynamic changes in gene expression that are associated with airway repair in response to physical injury. Gene expression changes in the airway wall following bronchial brush biopsy were profiled in anaesthetised sheep. The experimental design featured sequential studies in the same animals (n=8) over the course of a week and yielded data relating to the repair process at 6 hours, and 1, 3 and 7 days after injury. Notable features of the transcriptional response included the early and sustained preponderance of down-regulated genes associated with angiogenesis and immune cell activation, selection and differentiation. Later features of the repair response included the up-regulation of cell cycle genes at d1 and d3, and the later pronounced up-regulation of extracellular matrix-related genes at d3 and d7. It is possible to follow the process of airway wall repair in response to physical injury in the same animal over the course of time. Transcriptional changes featured coordinate expression of functionally related genes in a reproducible manner both within and between animals. This characterisation will provide a foundation against which to assess the perturbations that accompany airway disease pathologies of comparative relevance. Keywords: response to airway injury Each sheep was subjected to a protocol which involved the procedure of endobronchial brush biopsy (BBr) being performed, under anaesthesia, on three occasions, with two separate airway sites being subjected to brushing on each occasion. Two sheep were subjected to BBr seven days, three days and six hours prior to euthanasia, two sheep at seven days, three days and one day prior to euthanasia, two sheep at seven days, one day and six hours prior to euthanasia and two sheep at three days, one day and six hours prior to euthanasia. At post mortem examination (PME) each time point was therefore represented by material derived from six sheep. Airway tissue from a naM-CM-/ve site (from a segment not subjected to BBr) was also collected from each sheep at necropsy.
2013-05-27 | E-GEOD-37086 | biostudies-arrayexpress
Project description:Transcriptional profiling of HMB-treated (24h) differentiating equine satellite cells (3rd day of differentiation) exposed to hydrogen peroxide (1h; last hour of pre-incubation with HMB) compared to control HMB-untreated cells. Goal was to determine the effects of HMB pre-incubation on miRNA expression in equine satellite cells exposed to hydrogen peroxide.
2018-04-03 | GSE73779 | GEO
Project description:In vivo, satellite cells (SCs) are essential for skeletal muscle repair. However, in vitro investigation of SC function is challenged by isolation-induced SC activation, loss of the native quiescent state, and differentiation to myoblasts. This study applies tissue-engineered human skeletal muscle to track myoblast deactivation to 3D-SCs, which bear a quiescent phenotype, as well as examine melittin-induced injury response.
2021-11-11 | GSE188215 | GEO
Project description:Cachexia, a complex catabolic state, frequently accompanies pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer-related death in the US. We previously showed in a murine PDAC model that leucine supplementation improves muscle protein synthesis, but unfortunately also enhances PDAC cell growth, through activation of the mechanistic target of rapamycin (mTOR) signaling pathway. Utilizing the same murine PDAC model, herein we test the hypothesis that the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) enhances muscle protein synthesis but (unlike leucine) suppresses PDAC cell growth. Male C57BL/6 mice received either control diet (n=60) or a diet-induced obesity (DIO) regimen (n=60) for 10 weeks, then were subcutaneously injected (right flank) with Panc02 PDAC cells and further randomized to continue their diets ± HMB supplementation and ± gemcitabine chemotherapy. We determined that: a) DIO, relative to control diet, significantly increased Panc02 tumor growth (nearly 4-fold) and impaired chemotherapeutic response to gemcitabine; b) HMB significantly increased muscle fiber size and muscle mTOR activity in both DIO- and control-fed mice; c) HMB decreased tumor growth and partially rescued gemcitabine responsiveness in DIO-fed mice, but had no antitumor effect in control mice; d) gene expression profiling and additional qPCR, immunohistochemistry and in vitro studies indicate DIO promotes an immunosuppressive tumor microenvironment that is normalized by treatment with HMB. These preclinical findings suggest that HMB has muscle-sparing and anti-tumor activities against PDAC in the context of obesity.
2018-12-30 | GSE120348 | GEO
Project description:Transcriptional profiling of HMB-treated (24h) differentiating equine satellite cells (3rd day of differentiation) exposed to hydrogen peroxide (1h; last hour of pre-incubation with HMB) compared to control HMB-untreated cells. Goal was to determine the effects of HMB pre-incubation on gene expression in equine satellite cells exposed to hydrogen peroxide.
2018-04-03 | GSE93025 | GEO
Project description:2-Hydroxy-4-methoxybenzophenone (HMB) is an approved Food and Drug Administration (FDA) over-the-counter Category I product considered to be a deterrent to ultraviolet (UV) radiation-induced skin cancer. HMB is used in pharmaceuticals, plastic products, fabric coatings, finishes, and cosmetics. Exposure to HMB occurs through both occupational and consumer routes. HMB is used in skin moisturizing products and sunscreen lotions. In plastics manufacturing, HMB is used in surface coatings and polymers including ABS resins, cellulosic esters, polyesters, polystyrenes, rubber, flexible and rigid vinyl, and vinylidene chloride. HMB readily penetrates the skin and bioaccumulates in lipid-rich tissues. Uptake from the gastrointestinal tract is rapid. This study will characterize the toxicologic and carcinogenic potential of HMB administered in dosed feed to Sprague-Dawley rats given its potential for widespread human exposure as a broad-spectrum sunscreen.
2022-06-01 | GSE146485 | GEO
Project description:Metabolic stress and changes in nutrient levels modulate many aspects of skeletal muscle function during aging and disease. Growth factors and cytokines secreted by skeletal muscle, known as myokines, are important signaling factors but it is largely unknown whether they modulate muscle growth and differentiation in response to nutrients. Here, we find that changes in glucose levels increase the activity of the glucose-responsive transcription factor MLX, which promotes and is necessary for myoblast fusion. MLX promotes myogenesis not via an adjustment of glucose metabolism but rather by inducing the expression of several myokines, including insulin like-growth factor-2 (IGF2), whereas RNAi and dominant-negative MLX reduce IGF2 expression and block myogenesis. This phenotype is rescued by conditioned media from control muscle cells and by recombinant IGF2, which activates the myogenic kinase Akt. Importantly, MLX null mice display decreased IGF2 induction and diminished muscle regeneration in response to injury, indicating that the myogenic function of MLX is conserved in vivo. Thus, glucose is a signaling molecule that regulates myogenesis and muscle regeneration via MLX/IGF2/Akt signaling.â??The data pproided are histome H4 acetlation data for MLX DN and MLX wt samples; 3 MLX DN H4 Ac Chip seq samples , 3 Inputs, 3 MLX WT H4 Ac samples and 3 WT inputs
2015-11-11 | E-GEOD-74678 | biostudies-arrayexpress
Project description:to determine whether hydroxymethyl butyrate alters PDAC response to anti-PD1 therapy, mice bearing PANC02 tumors were treated with anti-PD1 with or without HMB supplementation, gastroc mucsle was isolated from ctrl and HMB groups and analysed by microarray for HMB induced differences in gene expression
2021-12-29 | GSE178476 | GEO
Project description:Upon muscle injury the high mobility group box 1 (HMGB1) protein is up-regulated and secreted to initiate reparative responses. Here we show that HMGB1 controls myogenesis both in vitro and in vivo, during development and after adult muscle injury. HMGB1 expression in muscle cells is regulated at the translational level: the miRNA miR-1192 inhibits HMGB1 translation and the RNA-binding protein HuR promotes it. HuR binds to a cis-element, HuRBS, located in the 3'UTR of the HMGB1 transcript, and at the same time miR-1192 is recruited to an adjacent seed element. The binding of HuR to the HuRBS prevents the recruitment of Argonaute 2 (Ago2), overriding miR-1192-mediated translation inhibition. Depleting HuR reduces myoblast fusion and silencing miR-1192 re-establishes the fusion potential of HuR-depleted cells. We propose that HuR promotes the commitment of myoblasts to myogenesis by enhancing the translation of HMGB1 and suppressing the translation inhibition mediated by miR-1192. RNA content was extracted following immunoprecipitation of HuR using a monoclonal antibody (3A2) and the levels of mRNA were compared to an IgG control in order to determine which transcripts were enriched in the HuR ribonucleoprotein complex.
2013-08-14 | E-GEOD-49855 | biostudies-arrayexpress
Project description:Upon muscle injury the high mobility group box 1 (HMGB1) protein is up-regulated and secreted to initiate reparative responses. Here we show that HMGB1 controls myogenesis both in vitro and in vivo, during development and after adult muscle injury. HMGB1 expression in muscle cells is regulated at the translational level: the miRNA miR-1192 inhibits HMGB1 translation and the RNA-binding protein HuR promotes it. HuR binds to a cis-element, HuRBS, located in the 3'UTR of the HMGB1 transcript, and at the same time miR-1192 is recruited to an adjacent seed element. The binding of HuR to the HuRBS prevents the recruitment of Argonaute 2 (Ago2), overriding miR-1192-mediated translation inhibition. Depleting HuR reduces myoblast fusion and silencing miR-1192 re-establishes the fusion potential of HuR-depleted cells. We propose that HuR promotes the commitment of myoblasts to myogenesis by enhancing the translation of HMGB1 and suppressing the translation inhibition mediated by miR-1192. RNA content was extracted following immunoprecipitation of HuR using a monoclonal antibody (3A2) and the levels of mRNA were compared to an IgG control in order to determine which transcripts were enriched in the HuR ribonucleoprotein complex.
2013-08-14 | E-GEOD-49856 | biostudies-arrayexpress