Rattus norvegicus
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ABSTRACT:
PROVIDER: PRJNA328224 | ENA |
REPOSITORIES: ENA
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Project description:In variceal bleeding liver function deterioration is a major cause of death. The effects of bleeding on intrahepatic microvascular dysfunction, which contributes to liver injury in cirrhosis, are largely unknown. The aims of this study were to evaluate the impact of hemorrhage/resuscitation (H/R) on cirrhotic microcirculation, and whether simvastatin, a drug that improves liver microcirculation, has hepatoprotective effects. The study was performed in three groups of rats: controls, rats with biliary cirrhosis (CBDL) and CBDL rats pre-treated with 3 doses (5 mg*Kg-1*day-1) of simvastatin. Rats were submitted to H/R or sham procedure. Subsequently, livers were isolated and perfused for functional assessment of liver microcirculation. Liver transcriptome was assessed with microarrays. H/R significantly impaired endothelial-dependent vasorelaxation in cirrhotic (p=0.035) but not control livers. H/R induced a similar increase in ALT in control and cirrhotic rats, whereas the increase in AST was 10 times higher in cirrhotic than in control rats (p=0.007). Simvastatin prevented the impairment in endothelial-dependent vasorelaxation induced by H/R, and reduced by half the increase in ALT and AST (p<0.05). Transcriptomics showed a marked upregulation of genes related to inflammatory response after H/R in cirrhotic livers, but not in controls, and this was blunted by simvastatin. In conclusion, H/R aggravates liver microvascular dysfunction in cirrhosis, and upregulates liver inflammatory pathways. This does not occur in control livers. Simvastatin prevented H/R-induced liver endothelial dysfunction, and attenuated liver injury and liver inflammatory response, suggesting that it might have potential for protecting the cirrhotic liver during bleeding complications.
2016-12-22 | GSE84178 | GEO
Project description:We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation, however the mechanism(s) for the IL-6 protective effect is not fully known. We used microarrays to detail the global gene expression in response to T/HS and the effect of IL-6 on this model with and without pharmacologic blockade of Stat3-mediated IL-6 and identified distinct members of the inflammasome de-regulated during T/HS that normalized with IL-6 administration during resuscitation.
2011-03-16 | GSE27978 | GEO
Project description:We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation, however the mechanism(s) for the IL-6 protective effect is not fully known. We used microarrays to detail the global gene expression in response to T/HS and the effect of IL-6 on this model with and without pharmacologic blockade of Stat3-mediated IL-6 and identified distinct members of the inflammasome de-regulated during T/HS that normalized with IL-6 administration during resuscitation. Adult male rats were subjected to either sham procedure, a trauma plus hemorrhagic shock (T/HS) procedure, T/HS with IL-6 versus PBS during resuscitation, or pretreatment with pharmacologic blockade of Stat3-mediated IL6 via GQ-ODN and after procedural completion, animals were sacrificed and livers were taken and homegenized for RNA extraction and microarray analysis using Affymetrix Rat 230A GeneChipM-BM-. array
2011-03-16 | E-GEOD-27978 | biostudies-arrayexpress
Project description:Molecular Signatures of Trauma Hemorrhagic Shock-Induced Lung Injury: Hemorrhage- and Injury-Associated Genes
| PRJNA99631 | ENA
Project description:WTCCC3_Primary Biliary Cirrhosis Replication Post-QC
| EGAD00010000928 | EGA
Project description:Purpose: Cholestatic liver injury is associated with intrahepatic biliary fibrosis, which can progress to cirrhosis. Resident hepatic progenitor cells (HPCs) expressing Prominin-1 (Prom1/CD133) become activated and participate in the expansion of cholangiocytes known as the ductular reaction. Previously, we demonstrated that in biliary atresia, Prom1(+) HPCs are present within developing fibrosis and that null mutation of Prom1 significantly abrogates fibrogenesis. Here, we hypothesized that these activated Prom1-expressing HPCs promote fibrogenesis in cholestatic liver injury. Methods: Using Prom1CreERT2-nLacZ/+;Rosa26Lsl-GFP/+ mice, we traced the fate of Prom1-expressing HPCs in the growth of the neonatal and adult livers and in biliary fibrosis induced by bile duct ligation (BDL). Results: Prom1-expressing cell lineage labeling with Green Fluorescent Protein (GFP) on postnatal day 1 exhibited an expanded population as well as bipotent differentiation potential towards both hepatocytes and cholangiocytes at postnatal day 35. However, in the adult liver, they lost hepatocyte differentiation potential. Upon cholestatic liver injury, adult Prom1-expressing HPCs gave rise to both PROM1(+) and PROM1(-) cholangiocytes contributing to ductular reaction without hepatocyte or myofibroblast differentiation. RNA-sequencing analysis of GFP(+) Prom1-expressing HPC lineage revealed a persistent cholangiocyte phenotype and evidence of Transforming Growth Factor-b pathway activation. Conclusion: Our data indicate that Prom1-expressing HPCs promote biliary fibrosis by activation of myofibroblasts in cholestatic liver injury.
2020-06-30 | GSE144726 | GEO