Early Mouse Hepatic Stellate Cell Activation
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE51882 | GEO | 2014/01/01
SECONDARY ACCESSION(S): PRJNA225669
REPOSITORIES: GEO
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Project description:Early during culture of primary mouse HSCs gene expression changes. These expression alterations can be affected by treating cells with histone deacetylase inhibitor, valproic acid Primary mouse Hepatic stellate cells were cultured for short periods of time (4-16-64h) in presence or absence of valproic acid. Gene expression analysis (mouse Gene 1.0 ST arrays according to manufacturerM-bM-^@M-^Ys manual 701880Rev4 (Affymetrix, Santa Clara, CA)), in vitro stellate cell activation and inhibition of the activation by valproic acid treatment.
2014-01-01 | E-GEOD-51882 | biostudies-arrayexpress
Project description:Aims: To obtain small non-coding RNA expression profiles of short-term activated and long-term activated hepatic stellate cells (HSCs). To obtain small non-coding RNA expression profiles of small extracellular vesicles (sEVs) from short-term activated and long-term activated HSCs. Methods: Primary rat HSCs were isolated and cultured in vitro. To isolate HSC-derived sEVs, culture media (CMs) from Day 0 to Day 3 and Day 7 to Day 14 were collected. The sEVs from Day 0 to Day 3 HSC CMs were referred to as short-term activated HSC-sEVs (3dHSC-sEVs), and those from Day 7 to Day 14 HSC CMs were referred to as long-term activated HSC-sEVs (14dHSC-sEVs). Day 3 HSCs, Day 14 HSCs, and HSC-sEVs were collected and lysed in TRIzol (Life Technologies) for RNA sample preparation at the indicated time points.
2024-08-29 | E-MTAB-12764 | biostudies-arrayexpress
Project description:Wnt/β-catenin is involved in every aspect of embryonic development and in the pathogenesis of many human diseases, and is also implicated in organ fibrosis. However, the role of β-catenin-mediated signaling on liver fibrosis remains unclear. To explore this issue, the effects of PRI-724, a selective inhibitor of the cAMP-response element-binding protein-binding protein (CBP)/β-catenin interaction, on liver fibrosis were examined using carbon tetrachloride (CCl4)- or bile duct ligation (BDL)-induced mouse liver fibrosis models. Following repetitive CCl4 administrations, the nuclear translocation of β-catenin was observed only in the non-parenchymal cells in the liver. PRI-724 treatment reduced the fibrosis induced by CCl4 or BDL, accompanied by the suppression of S100A4 expression, a CBP/β-catenin transcript. C-82, an active form of PRI-724, inhibited the activation of isolated primary mouse quiescent hepatic stellate cells (HSCs) and promoted cell death in culture-activated HSCs. During the fibrosis resolution period, an increase in F4/80+ CD11b+ and Ly6Clow CD11b+ macrophages was induced by CCl4 and was sustained for two weeks thereafter, even after having stopped CCl4 treatment. PRI-724 accelerated the resolution of CCl4-induced liver fibrosis, and this was accompanied by increased matrix metalloproteinase (MMP)-9, MMP-2, and MMP-8 expression in intrahepatic leukocytes. These results suggest that the inhibition of CBP/β-catenin suppresses liver fibrosis through the inhibition of HSCs activation, the induction of activated HSC death, and the production of MMPs from macrophages. Thus, targeting the CBP/β-catenin interaction may become a new therapeutic strategy in treating liver fibrosis. We used microarrays to detail the global change of gene expression by PRI-724 (C-82)-treatment in culture-activated murine hepatic stellate cells.
2018-09-30 | GSE73603 | GEO
Project description:Liver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. The goal of the present study is to identify experimental conditions that can revert the activated status of human HSCs and to map the molecular events associated with this phenotype reversion by gene expression profiling Transcriptomic profiling of primary human quiescent HSCs (qHSCs), in vitro activated HSCs (aHSCs) and in vitro reverted HSCs (rHSCs). The cell types come from different donors (This is detailed in the original manuscript.).
2015-08-12 | E-GEOD-68001 | biostudies-arrayexpress
Project description:DZNeP is the inhibitor of Ezh2 and paly negative roles on activation of hepatic stellate cells. We used RNA sequencing to identify the effective genes of DZNeP in rat HSCs. The primary rat HSCs was isolated and purified from SD rats, and cultured in DMEM culture medium with 20% FBS for 24 hours. Then the rat HSCs was administrated with DZNeP at 1μM concentration, or with similar volume of DMSO as negative control. 48 hour later, the cells were harvested and cell lysis was subjected to RNA-sequencing. This study identified that DZNeP regulated HSC activation through upregulating the expression of many key anti-fibrotic factors including Tgfβ signaling inhibitor: Bambi; cell cycle inhibitors: p21, Gadd45s; and immunomodulatory cytokine IL10.
2020-09-30 | GSE121736 | GEO
Project description:We have established culture systems to generate liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) from hiPSCs. To characterize gene expression profiling in hiPSC-derived LSECs and HSCs, transcriptome analysis was performed.
2017-07-27 | GSE92771 | GEO
Project description:We identified the genomic characteristics of peritumoral hepatic stellate cells (HSCs) in HBV related HCC. Expression levels of 17160 genes were compared between quiescent and activated HSCs and cancer associated myofibroblasts (CAMFs) from three independent samples per group. We find that among all significant changed genes (≥2-fold change and p<0.05), there were only 188 upregulated and 467 downregulated genes in peritumoral HSCs compared to intratumoral CAMFs. Compared with quiescent HSCs, the same patients-derived culture activated HSCs yielded as many as 1485 upregulated and 1471 downregulated genes. Between peritumoral HSCs/intratumoral CAMFs and culture-activated HSCs , there are 4479 and 3540 upregulated genes, and 3691 and 3380 downregulated genes, respectively. Between peritumoral HSCs/intratumoral CAMFs and quiescent phenotype HSCs, there are 1032 and 994 upregulated genes, and 1654 and 1188 downregulated genes, respectively.
2019-01-03 | GSE124552 | GEO
Project description:Activated hepatic stellate cell (HSC) is the main myofibroblast cell in the liver fibrosis(LF). An important characteristic of the recovery of LF is not only the apoptosis of activated HSCs but also reversal of myofibroblast-like phenotype to a quiescent-like phenotype. Understanding the changes of secreted proteins in the reversion of activated HSCs may provide the broader view of cellular regulatory networks and discover candidate markers or targets for therapeutic strategies of LF. In this study, stable isotope labeling with amino acids (SILAC) combining with LTQ-FT mass spectrometer were performed on in vitro activated HSCs and reverted HSCs to obtain a proteomic view of secretory proteins. In total, 330 proteins showed significant differences in reverted HSCs. Among these, 109 up-regulated proteins were mainly involved in amino acid metabolism pathway and glucose metabolism pathway using GeneGO/MetaCore software, while 221 down-regulated proteins are closely associated with HSCs activation, such as cytoskeleton remodeling, chemokines and cell adhesion. Additionally, a set of novel proteins associated with HSCs activation and reversion were validated by Western blotting in the cell secretion and in the sera of LF, including Vitronectin, laminin beta 1(LAMB1) and Ubiquitin conjugation factor E4B(UBE4B). Our study provided the valuable insight into the mechanisms in the reversion of activated HSCs and identified some potential biomarkers of LF in clinical studies.
2014-08-11 | PXD000773 | Pride
Project description:Liver injury causes “transdifferentiation” of quiescent hepatic stellate cells (Q-HSCs) into wound repairing myofibroblasts (MF-HSCs), whose uncontrolled activation leads ultimately to liver fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood. Here, using a compendium of in vitro, ex vivo and in vivo models of fibrogenic liver injuries in addition to human liver samples, we report that O-linked β D N acetylglucosaminylation (O GlcNAcylation), a post-translational modification (PTM) considered as nutritional sensor, is increased during myofibroblastic activation of HSCs and is required for their pro-fibrotic activities. Mechanistically, a multi omics approach combining proteomic, epigenomic and transcriptomic data mining revealed that O GlcNAcylation controls the transcriptional program of MF-HSCs by targeting the key fibrogenic transcription factors Basonuclin 2 (BNC2) and TEA domain transcription factor 4 (TEAD4) together with the Yes associated protein 1 (YAP1) co-activator. Indeed, inhibition of protein O GlcNAcylation impedes their stability leading to decreased functionality of the BNC2/TEAD4/YAP1 complex towards promoting activation of fibrogenic transcriptional regulatory elements. Altogether, this study unravels the fibrogenic role of protein O-GlcNAcylation identifying a vulnerable regulatory process in activated HSCs.
2024-05-21 | PXD045860 | Pride
Project description:The molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. In addition, the gene expression changes associated with activation of primary human hepatic stellate cells, a key event during fibrogenesis, remain poorly characterized. Here, we provide the transriptomic profile underpinning the healthy phenotype of human hepatocytes, liver sinusoidal endothelial cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as activated HSCs (aHSCs) We assess the transcriptome for purified, non-cultured human hepatocytes, liver sinusoidal cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as culture-activated HSCs (aHSCs). Hepatocytes (n=2 donors), LSECs (n=3), qHSCs (n=3) and in vitro activated HSCs (n=3; from the same donors as the qHSCs and LSECs) were used for this study.
2016-03-02 | E-GEOD-68000 | biostudies-arrayexpress