Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver
Antagonism of microRNA-122 in mice by systemically administered LNA-antimiR leads to up-regulation of a large set of predicted target mRNAs in the liver.
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View SamplesThe present study was constructed to confirm previous findings that mice on a high fat diet (HFD) treated by subcutaneous injection with exenatide (EXE) at 3g/kg once daily for 6 weeks develop exocrine pancreatic injury (Rouse et al. 2014). The present study included 12 weeks of EXE exposure at multiple concentrations (3, 10, or 30 g/kg) with multiple endpoints (histopathology evaluations, immunoassay for cytokines, immunostaining of the pancreas, serum chemistries and measurement of trypsin, amylase, and, lipase, and gene expression profiles). Time- and dose-dependent exocrine pancreatic injury was observed in mice associated with EXE exposure in a HFD environment. The time- and dose-dependent morphological changes identified in the pancreas involved acinar cell injury and death (autophagy, apoptosis, necrosis, and atrophy), cell adaptations (hypertrophy and hyperplasia), and cell survival (regeneration) accompanied with varying degrees of inflammatory response leading to secondary injury in pancreatic blood vessels, ducts, and adipose tissues. Gene expression profiles supported the presence of increased signaling for cell survival and altered lipid metabolism. The potential for EXE to cause acute or early chronic pancreatic injury was identified in a HFD environment. In human disease, the influence of pancreatitis risk factors or pre-existing chronic pancreatitis on this injury potential requires further investigation.
Extended exenatide administration enhances lipid metabolism and exacerbates pancreatic injury in mice on a high fat, high carbohydrate diet.
Sex, Specimen part
View SamplesMultipotent stromal cells (MSCs) are currently in clinical trials for a number of inflammatory diseases. Recent studies have demonstrated the ability of MSCs to attenuate inflammation in rodent models of acute lung injury (ALI) suggesting that MSCs may also be beneficial in treating ALI. To better understand how human MSCs (hMSCs) may act in ALI, the lungs of immunocompetent mice were exposed to lipopolysaccharide (LPS) and 4 hr later bone marrow derived hMSCS were delivered by oropharyngeal aspiration (OA). Administration of hMSCs significantly reduced the expression of pro-inflammatory cytokines, neutrophil counts and total protein in bronchoalveolar lavage. There was a concomitant reduction in pulmonary edema as indicated by a decrease in lung wet/dry weight ratio. The anti-inflammatory effects of hMSCs were not dependent on localization to the lung, as intraperitoneal administration of hMSCs also attenuated LPS-induced inflammation in the lung. Microarray analysis revealed significant induction of TNF--induced protein 6 (TSG-6) expression by hMSCs 12 hr after OA delivery to LPS-exposed lungs. Knockdown of TSG-6 expression in hMSCs by RNA interference abrogated most of their anti-inflammatory effects. In addition, intra-pulmonary delivery of recombinant human TSG-6 reduced LPS-induced inflammation in the lung. These results show that hMSCs recapitulate the observed beneficial effects of rodent MSCs in animal models of ALI and suggest that the anti-inflammatory properties of hMSCs in the lung are explained, at least in part, by activation of hMSCs to secrete TSG-6.
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Sex, Specimen part, Treatment
View SamplesQuantitative assays for human DNA and mRNA were used to examine the paradox that intravenously (IV) infused human multipotent stromal cells (hMSCs) can enhance tissue repair without significant engraftment. After 2 X 106 hMSCs were IV infused into mice, most of the cells were trapped as emboli in lung. The cells in lung disappeared with a half-life of about 24 hr but < 1,000 cells appeared in 6 other tissues. The hMSCs in lung up-regulated expression of multiple genes with a large increase in the anti-inflammatory protein TSG-6. After myocardial infarction, IV hMSCs but not hMSCs transduced with TSG-6 siRNA decreased inflammatory responses, reduced infarct size, and improved cardiac function. IV administration of recombinant TSG-6 also reduced inflammatory responses and reduced infarct size. The results suggest improvements in animal models and patients after IV infusions of MSCs are at least in part explained by activation of MSCs to secrete TSG-6.
Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6.
Specimen part, Disease
View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Genetic information
View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Genetic information
View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Genetic information
View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Genetic information
View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Genetic information
View SamplesSky1 is a Saccharomyces cerevisiae rich serine-arginine (SR) protein-specific kinase and its enzymatic activity is essential in the cytotoxicity caused by cisplatin, although the molecular mechanisms supporting this function are not understood. We present a transcriptome analysis discriminating between RNA changes induced by cisplatin which are dependent or independent of the Sky1 function.
Sky1 regulates the expression of sulfur metabolism genes in response to cisplatin.
Genetic information
View Samples