Carbon tetrachloride (CCl4) induced liver fibrosis
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE207855 | GEO | 2022/08/19
REPOSITORIES: GEO
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Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver. To induce chronic liver fibrosis, seven-week-old mice received 0.6 ml/kg body weight of carbon-tetrachloride (CCl4) dissolved in corn-oil by intraperitoneal (i.p.) injection, twice a week for 10 weeks (n=3). As a control, same number of mice was injected with equal volume of corn-oil for 10 weeks.
2016-03-22 | E-GEOD-77271 | biostudies-arrayexpress
Project description:Liver fibrosis was found to be existed in all kinds of chronic liver diseases. Many studies suggested that DNA methylation was related with the pathogenesis of liver fibrosis. The aim of this study was to quantitatively detect DNA methylation changes in the whole genome in fibrotic liver tissues. Carbon tetrachloride (CCl4) was used to induce male mice liver fibrosis by intraperitoneal injection for 4 weeks. A genome-wide methylome analysis was performed using 850K BeadChips assays. The methylation status of 27 CpG dinucleotides located in 3 genes was detected by pyrosequencing to confirm chips data accuracy, and their mRNA expressions were examined by RT-qPCR methods. A total of 130,068 differentially methylated sites (DMS, 58,474 hypermethylated and 71,594 hypomethylated) between fibrotic liver tissues and control mice liver tissues were identified by the 850k BeadChips array. They distribute in each chromosome. Recognition of apoptotic cell, Notch and p38MAPK et al activities were significantly enriched in the Gene Ontology (GO) analyses. Cholesterol metabolism, bile secretion and more biosynthesis and metabolism pathway were enriched in KEGG pathway analyses. Many classical pathways of fibrogenesis and liver activity, as well as more biosynthetic and metabolic pathways, were found to be related to methylation changes. Our result facilitates future research for clinical application.
2023-01-11 | GSE193182 | GEO
Project description:To investigate the differences in microRNA expression profiles between fibrotic and normal livers, we performed microRNA microarrays for total RNA extracts isolated from mouse livers treated with carbontetrachloride (CCl4) or corn-oil for 10 weeks (n=3/group). MicroRNAs were considered to have significant differences in expression level when the expression difference showed more than two-fold change between the experimental and control groups at p<0.05. We found that 12 miRNAs were differentially expressed in CCl4-induced fibrotic liver.
2016-03-22 | GSE77271 | GEO
Project description:Abstract from Knabel et al. PLoS One (2015): Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature of many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress target gene expression and the development of miRNA-based therapeutics is being actively pursued for a diverse array of diseases. Because a single miRNA can target multiple genes, often within the same pathway, variations in the level of individual miRNAs can potently influence disease phenotypes. Members of the miR-29 family, which include mir29a, miR-29b and miR-29c, are strong inhibitors of ECM synthesis and fibrosis-associated decreases in miR-29 have been reported in multiple organs. We observed downregulation of miR-29a/b/c in fibrotic livers of carbon tetrachloride (CCl4) treated mice as well as in isolated human hepatocytes exposed to the pro-fibrotic cytokine TGF-β. Importantly, we demonstrate that a single systemic injection of a miR-29a expressing adeno-associated virus (AAV) can prevent and even reverse histologic and biochemical evidence of fibrosis despite continued exposure to CCl4. The observed therapeutic benefits were associated with AAV transduction of hepatocytes but not hepatic stellate cells, which are the main ECM producing cells in fibroproliferative liver diseases. Our data therefore demonstrate that delivery of mir-29 to the hepatic parenchyma using a clinically relevant gene delivery platform protects injured livers against fibrosis and, given the consistent fibrosis-associated downregulation of miR-29, suggests AAV-miR-29 based therapies may be effective in treating a variety of fibroproliferative disorders. The Taqman MicroRNA Array (Taqman Array Rodent MicroRNA A Cards v2.0, ABI) was run, using manufacturer's protocols, on 3 groups of mice with varying amounts fibrotic injury. The groups include carbon tetrachloride intraperitinially injected bi-weekly for 1, 4, and 8 weeks with n=4, 3, and 2 respectively for each group. The RNA was isolated from whole liver using the MiRvana miRNA Isolation Kit (Ambion) according to manufacturer's protocols. The fold_change.txt contains the following data columns; ID_Ref: mmu-miR being quantified not-treated (FC): Fold Change compared to not-treated group using Geometric mean normalization 1 week (FC): Fold Change compared to not-treated group using Geometric mean normalization 4 weeks (FC): Fold Change compared to not-treated group using Geometric mean normalization 8 weeks (FC): Fold Change compared to not-treated group using Geometric mean normalization
2015-02-25 | E-GEOD-66278 | biostudies-arrayexpress
Project description:Liver fibrosis is a multifactorial trait that develops in response to chronic liver injury. Our aim was to characterize the genetic architecture of carbon tetrachloride (CCl4)-induced liver fibrosis using the Hybrid Mouse Diversity Panel (HMDP), a panel of over 100 genetically distinct mouse strains optimized for genome wide association studies and systems genetics. Chronic liver injury was induced by CCl4 injections twice weekly for six weeks. 437 mice received CCl4 and 256 received vehicle, after which animals were sacrificed for liver histology and gene expression. Using automated digital image analysis, we quantified fibrosis as the collagen proportionate area % (CPA%) of the whole section, excluding normal collagen. We discovered broad variation in fibrosis among the HMDP strains, demonstrating a significant genetic influence on this trait, with an estimated heritability (H2) of 44%. Genome-wide association analyses revealed significant and suggestive loci underlying susceptibility to fibrosis, some of which overlapped with loci identified in mouse crosses and human population studies. Liver global gene expression was assessed by RNA sequencing, and gene set enrichment analyses identified the underlying pathways, of which stellate cell involvement was prominent. We also performed expression quantitative trait locus analyses to identify strong causal candidate genes. Our results provide a rich resource for the design of experiments to understand mechanisms underlying fibrosis and for rational strain selection when testing anti-fibrotic drugs.
2021-03-22 | GSE152329 | GEO
Project description:Abstract from Knabel et al. PLoS One (2015): Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature of many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short, non-coding RNAs that post-transcriptionally repress target gene expression and the development of miRNA-based therapeutics is being actively pursued for a diverse array of diseases. Because a single miRNA can target multiple genes, often within the same pathway, variations in the level of individual miRNAs can potently influence disease phenotypes. Members of the miR-29 family, which include mir29a, miR-29b and miR-29c, are strong inhibitors of ECM synthesis and fibrosis-associated decreases in miR-29 have been reported in multiple organs. We observed downregulation of miR-29a/b/c in fibrotic livers of carbon tetrachloride (CCl4) treated mice as well as in isolated human hepatocytes exposed to the pro-fibrotic cytokine TGF-β. Importantly, we demonstrate that a single systemic injection of a miR-29a expressing adeno-associated virus (AAV) can prevent and even reverse histologic and biochemical evidence of fibrosis despite continued exposure to CCl4. The observed therapeutic benefits were associated with AAV transduction of hepatocytes but not hepatic stellate cells, which are the main ECM producing cells in fibroproliferative liver diseases. Our data therefore demonstrate that delivery of mir-29 to the hepatic parenchyma using a clinically relevant gene delivery platform protects injured livers against fibrosis and, given the consistent fibrosis-associated downregulation of miR-29, suggests AAV-miR-29 based therapies may be effective in treating a variety of fibroproliferative disorders.
2015-02-25 | GSE66278 | GEO
Project description:Long non-coding RNAs (lncRNAs) are involved in numerous biological functions and pathological processes. In this study, we have identified a novel lncRNA ENSMUST00000147617, named Highly Expressed in Liver Fibrosis (lnc-HELF), which is remarkably up-regulated in mouse and human fibrotic livers. To identify the roles of lnc-HELF in liver fibrosis, we performed RNA-seq to analyze the effect of lnc-HELF deficient on CCl4-induced liver fibrosis. The mice were divided in three groups: mice treated with CCl4 in combination with injection of AAV8-NC (NC_CCl4, n=3), mice treated with CCl4 in combination with injection of AAV8-shRNA-lncHELF1# (sh1_CCl4, n=3) and mice treated with CCl4 in combination with injection of AAV8-shRNA-lncHELF2# (sh2_CCl4, n=3).
2023-10-05 | GSE182485 | GEO
Project description:Gene-expression profiles of liver tissue of cabon tetrachloride (CCl4)-treated mouse and the effect of erlotinib Hepatocellular carcinoma (HCC) is the sixth most common solid tumor worldwide and the third leading cause of cancer-related death. Given the lack of successful treatment options, chemoprevention in high-risk patients has been proposed as an alternative strategy. Mounting evidence supports a role for epidermal growth factor (EGF) during chronic liver disease and hepatocellular transformation. We address the hypothesis that blocking the EGF-EGF receptor (EGFR) pathway may be an effective strategy for inhibiting fibrogenesis and hepatocarcinogenesis. A rat model of diethylnitrosamine (DEN)-induced cirrhosis was used to examine the effects of erlotinib on underlying chronic liver disease and HCC formation. The DEN-induced rat model closely resembles disease progression in humans both pathologically and molecularly. Erlotinib significantly prevented the development of HCC tumor nodules in a dose-dependent fashion. Further, erlotinib inhibited the activation of hepatic stellate cells and prevented fibrogenesis. Erlotinib also reduced hepatotoxicity and improved liver function. Finally, a gene expression signature predictive of poor survival in human cirrhosis patients was reversed in response to erlotinib. Our data demonstrate for the first time that EGFR inhibition prevents liver fibrogenesis. Further, our results suggest that erlotinib is a potentially effective HCC chemoprevention strategy through inhibition of cirrhosis progression which can be monitored at the molecular level. Animals received humane care according to the criteria outlined in the M-bM-^@M-^\Guide for the Care and Use of Laboratory AnimalsM-bM-^@M-^] of the National Academy of Sciences. All animals were maintained in accordance with the institutional guidelines of the Massachusetts General Hospital Subcommittee on Research Animal Care. Strain A/J male mice (Jackson Laboratory, Bar Harbor, ME) were treated three times a week for 18 weeks with either 0.1cc of a 40 percent solution of CCl4 (Sigma) in olive oil or with vehicle control by oral gavage. Mice were sacrificed at 19 weeks after a one-week washout to eliminate acute effects of CCl4. The liver was sectioned and fixed in phosphate-buffered 10% formaldehyde for histological analysis. The remaining portions of the liver were collected in RNase-free tubes and snap-frozen in liquid nitrogen. Frozen tissues were stored at -80M-BM-0C until use.
2014-02-28 | E-GEOD-27640 | biostudies-arrayexpress
Project description:This study aimed to investigate the protective mechanisms of helenalin on hepatic fibrosis,Rats were intragastrically administrated with 50% CCl4 for 9 weeks to induce liver fibrosis, followed by various medicines for 6 weeks. The transcriptomic analysis was performed in liver tissues by RNA-seq.
2021-11-25 | GSE189402 | GEO
Project description:Gene-expression profiles of liver tissue of cabon tetrachloride (CCl4)-treated and control mice were obtained before and after organotypic ex vivo tissue culture. keywords: liver tissue, mouse, gene-expression microarray, Illumina, ex vivo tissue culture
2016-12-16 | GSE71379 | GEO