E-GEOD-38648
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA168305
PROVIDER: E-GEOD-38648 | ExpressionAtlas | 2015-07-08
REPOSITORIES: ExpressionAtlas
Similar Datasets
Project description:Deactivation of Hepatic Stellate Cells during Liver Fibrosis Resolution in Mice
| PRJNA168305 | ENA
Project description:It is known that administration of MCD induces a severe state of hepatic fibrosis in mice. Recently, many microRNAs (miRNAs) with pro- or anti-fibrotic properties have been identified during hepatic fibrosis. To attempt to elucidate molecular mechanism of hepatic fibrosis involved in miRNA fnction, we performed comprehensive analysis of miRNA expression by microarray using RNAs prepared from liver of wild-type mice fed with normal diet (ND) or MCD.
2023-12-06 | GSE249486 | GEO
Project description:Increased liver de novo lipogenesis (DNL) is a hallmark of nonalcoholic steatohepatitis (NASH). A key enzyme controlling DNL upregulated in NASH is ATP citrate lyase (ACLY). In mice, inhibition of ACLY reduces liver steatosis, ballooning and fibrosis and inhibits activation of hepatic stellate cells. Glucagon like peptide-1 receptor (GLP-1R) agonists lower body mass, insulin resistance and steatosis without improving fibrosis. Here, we find that combining an inhibitor of liver ACLY, bempedoic acid, and the GLP-1R agonist liraglutide reduces liver steatosis, hepatocellular ballooning, and hepatic fibrosis in a mouse model of NASH. Liver RNA analyses revealed additive downregulation of pathways that are predictive of NASH resolution, reductions in the expression of prognostically significant genes compared to clinical NASH samples, and a predicted gene signature profile that supports fibrosis resolution. These findings support further investigation of this combinatorial therapy to treat obesity, insulin resistance, hypercholesterolemia, steatohepatitis, and fibrosis in people with NASH.
2023-08-09 | GSE240409 | GEO
Project description:Increased liver de novo lipogenesis (DNL) is a hallmark of nonalcoholic steatohepatitis (NASH). A key enzyme controlling DNL upregulated in NASH is ATP citrate lyase (ACLY). In mice, inhibition of ACLY reduces liver steatosis, ballooning and fibrosis and inhibits activation of hepatic stellate cells. Glucagon like peptide-1 receptor (GLP-1R) agonists lower body mass, insulin resistance and steatosis without improving fibrosis. Here, we find that combining an inhibitor of liver ACLY, bempedoic acid, and the GLP-1R agonist liraglutide reduces liver steatosis, hepatocellular ballooning, and hepatic fibrosis in a mouse model of NASH. Liver RNA analyses revealed additive downregulation of pathways that are predictive of NASH resolution, reductions in the expression of prognostically significant genes compared to clinical NASH samples, and a predicted gene signature profile that supports fibrosis resolution. These findings support further investigation of this combinatorial therapy to treat obesity, insulin resistance, hypercholesterolemia, steatohepatitis, and fibrosis in people with NASH.
2023-08-09 | GSE240406 | GEO
Project description:Over expression of PDGF-C in mouse liver resulted in the progression of hepatic fibrosis, steatosis and the development of HCC; this mouse model closely resembles the human HCC that is frequently associated with hepatic fibrosis. Peretinoin (generic name; code, NIK-333), developed by the Kowa Company, (Tokyo, Japan), is an oral acyclic retinoid (ACR) with a vitamin A-like structure that targets the retinoid nuclear receptor. Peretinoin effectively inhibits the progression of hepatic fibrosis and tumors in Pdgf-c Tg mice. Gene expression profiling was evaluated during the progression of hepatic fibrosis and tumors. After weaning at week 4, Pdgf-c Tg or non-transgenic WT mice were fed a basal diet or a diet containing+0.06% peretinoin respectively. At week 20, mice were sacrificed for the analysis of progression of hepatic fibrosis. At week 48, mice were sacrificed for the analysis of the development of hepatic tumors.
2012-10-03 | E-GEOD-31431 | biostudies-arrayexpress
Project description:We profile the transcriptomes of ~30,000 mouse single cells to deconvolve the hepatic mesenchyme in healthy and fibrotic liver at high resolution. We reveal spatial zonation of hepatic stellate cells across the liver lobule, designated portal vein-associated HSC and central vein-associated HSC, and uncover an equivalent functional zonation in a mouse model of centrilobular fibrosis. Our work illustrates the power of single-cell transcriptomics to resolve key collagen-producing cells driving liver fibrosis with high precision.
2019-11-01 | GSE137720 | GEO
Project description:To explore key features associated with the resolution process in liver fibrosis, we here applied a previously reported murine liver fibrosis resolution model, in which wild-type mice were injected with carbon tetrachloride (CCl4) diluted in olive oil (1:9) intraperitoneally (0.6 μL/g body weight; Sigma) thrice per week for four weeks, and then observed without administration for 96 hours. We conformed that liver fibrosis was resolved in these mice (RES) after 96 hours from the last injection, along with upregulation of hepatic MMPs. Among CD45+ non-parenchymal cells, we noted that most MMPs were expressed by CD11b+ cells. To reveal the transcriptome profiling-based subtypes of CD45+ CD11b+ cells present during the liver fibrosis resolution, we performed scRNA-seq analysis. With corresponding cells from uninjured non-fibrotic wild-type mice as controls (Ctrl), a total of 7969 cells were clustered into 18 clusters based on the gene signatures. We revealed that a unique cluster of Ly6c2-low expressing CD11b+ macrophages (cluster Mac3) were enriched in livers resolved from CCl4-induced liver fibrosis. Comprehensive analysis of expression of known toll-like receptors in myeloid clusters demonstrated a unique upregulation of Tlr4 in Mac3. Moreover, only Ly6c2-low myeloid cells belonging to Mac 3 also demonstrated up-regulation of the expression of genes involved in extracellular matrix remodelling, post-phagocytosis, anti-inflammatory and antifibrotic pathways, and combined properties of both M1 and M2 features. Additionally, many of these genes highly expressed in Mac 3 were associated with the TLR4 pathway.
2023-02-14 | GSE189606 | GEO
Project description:Hepatic fibrosis is the common end stage to a variety of chronic liver injuries and is characterized by an excessive deposition of extracellular matrix (ECM), which disrupts the liver architecture and impairs liver function. The fibrous lesions are produced by myofibroblasts, which differentiate from hepatic stellate cells (HSC). The myofibroblasts transcriptional networks remain poorly characterized. Previous studies have shown that the Forkhead box F1 (FOXF1) transcription factor is expressed in HSCs and stimulates their activation during acute liver injury; however, the role of FOXF1 in the progression of hepatic fibrosis is unknown. In the present study, we generated αSMACreER;Foxf1fl/fl mice to conditionally inactivate Foxf1 in myofibroblasts during carbon tetrachloride-mediated liver fibrosis. Foxf1 deletion increased collagen depositions and disrupted liver architecture. Timp2 expression was significantly increased in Foxf1-deficient mice while MMP9 activity was reduced. RNA sequencing of purified liver myofibroblasts demonstrated that FOXF1 inhibits expression of pro-fibrotic genes, Col1α2, Col5α2, and Mmp2 in fibrotic livers and binds to active repressors located in promotors and introns of these genes. Overexpression of FOXF1 inhibits Col1a2, Col5a2, and MMP2 in primary murine HSCs in vitro. Altogether, FOXF1 prevents aberrant ECM depositions during hepatic fibrosis by repressing pro-fibrotic gene transcription in myofibroblasts and HSCs.
2019-02-05 | GSE123726 | GEO
Project description:Liver fibrosis is a reversible wound-healing response to liver injury and hepatic stellate cells (HSCs) are central cellular players that mediate hepatic fibrogenesis. However, the molecular mechanisms that govern this process remain unclear. Here, we reveal a novel cistromic circuit in HSCs comprising the vitamin D receptor (VDR) and SMAD transcription factors that restrains the intensity of hepatic fibrogenesis. Ligand-activated VDR suppresses TGFβ1-induced pro-fibrotic gene expression in HSCs. Administration of a vitamin D analogue, calcipotriol, diminishes the fibrotic response in a mouse model of liver fibrosis, while VDR knockout mice spontaneous develop extensive hepatic fibrosis by age 6 months. Using ChIP-Seq, we find that the anti-fibrotic properties of VDR are due to crosstalk with SMAD, mediated by their co-occupancy of DNA-binding sites on pro-fibrotic genes. Specifically, SMAD binding potentiates local chromatin accessibility to enhance VDR recruitment at the same cis-regulatory elements, which reciprocally antagonizes the interaction between SMAD3 and chromatin and limits the assembly of transcriptional activation complexes at fibrotic genes, a process that is enhanced by the presence of VDR agonists. These results not only establish this coordinated VDR/SMAD cistromic circuit as a master regulator of hepatic fibrogenesis, but also support VDR as a potential drug target to ameliorate liver fibrosis. Identification of VDR, SMAD3 and H3 binding sites in human stellate LX2 cells that were pre-treated with calcipotriol (100nM) for 16 hrs (where calcipotriol treatment is indicated) followed by incubation of calcipotriol (100nM) or TGFβ1 (1ng/ml) for another 4 hours (where indicated).
2013-04-29 | E-GEOD-38103 | biostudies-arrayexpress
Project description:Hepatic fibrosis is a dynamic process characterized by the net accumulation of extracellular matrix resulting from chronic liver injury such as nonalcoholic steatohepatitis. During the pathogenesis of hepatic fibrosis, activation of hepatic stellate cells (HSCs) causes transdifferentiation of quiescent cells into proliferative and fibrogenic myofibroblasts. In the present study, we developed a novel RORα-selective ligand, ODH-08, based on the modification of JC1-40, a previously reported N-methylthiourea analog. Administration of ODH-08 to Western diet (WD)-fed mice improved the signs of hepatic fibrosis: decreased hepatic collagen deposition and suppression of the expression of fibrogenic markers. ODH-08 inhibits the TGF1-induced fibrogenic activation of HSCs through suppression of the TGFβ1–SMAD signaling pathway, which represents a novel mechanism for the antifibrogenic effect of RORα. Thus, ODH-08 appears to be a promising antifibrotic agent to treat hepatic fibrosis. We performed a microarray analysis in the liver tissue of ODH-08-treated WD-fed mice to anlyse differentially expressed genes under ODH-08 administration. The control group was vehicle-treated WD-fed mice.
2024-03-01 | GSE250531 | GEO