Transcriptome changes after TSG-6 treatment of mouse liver fibrosis.
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ABSTRACT:
PROVIDER: PRJNA498069 | ENA |
REPOSITORIES: ENA
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Project description:Our previous studies revealed that exogenous administration of TSG-6 can ameliorate liver fibrosis. We next analyzed liver transcriptome changes after TSG-6 treatment in order to explore possible therapeutic changes.
2021-10-23 | GSE121669 | GEO
Project description:Phloridzin reveals new treatment strategies for liver fibrosis
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Project description:Liver fibrosis, is an urgent public health problem and is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of messenger RNA (mRNA) and long non-coding RNA (lncRNA) in different groups of liver tissues, and screened for differentially expressed genes, as well as performed gene co-expression analysis of the differential lncRNAs and mRNAs. The results showed that compared with the model group, the phloridzin treated groups showed a significant decrease in collagen deposition, and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell-substrate junctions, and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism and related changes in biomechanics.
2022-08-03 | GSE205540 | GEO
Project description:TNFα-stimulated gene 6 (TSG-6) is an anti-inflammatory protein. In human epidermis, TSG-6 is secreted in extracellular matrix where it interacts with hyaluronan (HA). However, their functions are not well understood. In this study, immortalized N/TERT keratinocytes were edited by CRISPR/Cas9, used to reconstruct in vitro epidermis (RHE) and stimulated or not with interleukins 4 and 13 for 48h to mimic atopic dermatitis (AD). Two TSG-6-/- clones (respectively TSG-6-/- (a) and TSG-6-/- (b)) harboring major deletions in both alleles were selected and compared to TSG-6+/+ cells. Epidermis reconstructed from TSG-6-/- (a) and TSG-6-/- (b) exhibit normal differentiation process and morphology but show an increased HA leakage in the underlying culture medium of both TSG-6-/- RHE compared to TSG-6+/+ tissues, especially in conditions that mimic AD. While IL-4/13 treatment of RHE induces regulation of genes associated with AD, the absence of TSG-6 don’t seem to show any major transcriptomic regulation.
2021-12-30 | E-MTAB-10095 | biostudies-arrayexpress
Project description:mRNA sequencing after BMSC treatment of BDL-induced liver fibrosis
| PRJNA1157746 | ENA
Project description:BACKGROUND AND AIMS: Perianal fistula represents one of the most important complications in Crohn’s Disease (CD). Epithelial-to-mesenchymal transition (EMT) has been demonstrated to play a major role in the pathogenesis, however the mechanisms driving EMT need to be clarified. Significant alterations in the tissue structural composition occur in the fistula, but how these changes promote EMT was not addressed. We aim to explore the relevance of TSG-6, a stabilizer of extracellular matrix, in the fistula pathogenesis. METHODS: Intestinal surgical specimens from perianal fistula tissue and surrounding region of fistulizing CD were analyzed histologically and by RNA sequencing (RNA-seq). Significantly modulated genes and TSG-6 expression were validated by RT-PCR, WB and immunofluorescence assays [N=20]. TSG-6 expression was reconstituted in Caco-2 cell line and primary perifistula-derived fibroblasts, and proliferative and migratory assays were performed. RESULTS: A marked different organization of extracellular matrix was found across fistula and perifistula regions with an increased expression of integrins, hyaluronan synthases, TSG-6 and MMPs in the fistula. TSG-6 overexpression in Caco-2 cells reduced proliferation, promoted the EMT transcription factor SNAIL, and, in co-stimulation with TGFβ1, migration. The acquisition of TSG-6 increased SNAI1 and hyaluronan synthases levels, and led to activated phenotype of perifistula-derived fibroblasts. Positive Pearson correlation was observed between TSG-6 expression and mechanosensitive proteins in fistula tissue. CONCLUSIONS: By mediating changes in the extracellular matrix organization, TSG-6 triggers the EMT transcription factor SNAIL through the activation of mechanosensitive proteins. These data point to TSG-6 as a new potential target for the treatment of perianal fistula.
2023-01-04 | GSE157020 | GEO
Project description:Background & Aims: Persistent activation of hepatic stellate cells (HSCs) drives liver fibrosis, marked by myofibroblast activation (MFA) and epithelial-mesenchymal transition (EMT). Strategies to prevent or reverse this will be critical to treat liver fibrosis successfully. We previously showed that full-term, cell-free human amniotic fluid (cfAF) inhibits MFA and EMT in fibroblasts in vitro. We hypothesize that cfAF treatment can attenuate HSC activation and limit liver fibrosis. Methods: HSC activation was assessed using murine models of acute (DMN) and chronic (CCl4) liver damage, three-dimensional hepatic spheroids, and HSC cultures. EMT and MFA were induced in vitro using ethanol (spheroids) or TGFβ (HSCs) and evaluated via scratch assays, multi-omics approaches, and RNA/protein analyses. Results: cfAF treatment prevented weight loss in mice with chronic liver damage without adverse events. Histological analysis revealed a modest reduction in fibrosis with preserved liver architecture in both chronic and acute murine liver damage models. Gene expression profiling and immunostaining indicated cfAF administration to CCl4-treated mice led to reduced EMT- and MFA-related biomarkers along with changes in transcripts associated with liver metabolism, immune regulatory pathways, and cell signaling. In hepatic spheroids exposed to ethanol cfAF treatment lowered COL1A1 protein levels and smooth muscle actin (SMA) RNA abundance in a dose-dependent manner. Treating primary or LX2 hepatic stellate cells with cfAF strongly represses EMT, and multi-omics analyses revealed that it also attenuates TGFβ-induced MFA and the inflammatory phenotype. Thus cfAF treatment prevents liver fibrosis by safeguarding hepatic stellate cell activation. Conclusions: cfAF treatment limits liver fibrosis by repressing HSC activation in liver fibrosis models. These findings suggest cfAF may be a safe and effective therapy for reducing liver fibrosis and preventing the development of cirrhosis and/or hepatocellular carcinoma.
2025-03-17 | GSE290015 | GEO
Project description:Liver fibrosis is an urgent clinical problem without effective treatment. Herein, we conducted a high-content screening on a natural “privileged” diterpenoid library to identify a potent anti-liver fibrosis lead DP. Leveraging photoaffinity labeling approach, apolipoprotein L2 (APOL2), an ER-rich protein, was identified as the direct target of DP. APOL2 is mainly expressed in activated hepatic stellate cells (HSCs) and could activate HSCs to synthesize ECM proteins. It can be induced by TGF-β1 and be antagonized by DP. Mechanistically, upon TGF-β1stimulation, APOL2 binds ER Ca2+ pump SERCA2 to trigger ER stress, elevating its downstream PERK-HES1 axis to promote liver fibrosis, mildly dependent on the canonical TGF-β/Smad signaling. As a result, ablation of APOL2 significantly alleviated TGF-β1-stimulated HSCs activation, and abolished anti-fibrosis effect of DP. Our findings not only define APOL2 as a novel therapeutic target for liver fibrosis, but also highlight DP as a promising lead for treatment of this symptom.
2024-08-13 | PXD047924 | Pride
Project description:To confirm the mechanism of miR-29a in liver fibrosis healing, we have employed whole genome microarray expression profiling as a discovery platform to identify genes. CCl4 and TAA liver fibrosis model mouse were used for this experiment. After five weeks liver fibrosis induction period, mouse have been observed for one week (1w) or two weeks (2w) and negative control nucleotide (N.C) or miR-29a were injected every 3 days on this period. We used CCl4 1w N.C (n = 1), 1w miR-29a (n = 1), 2w N.C (n = 1), 2w miR-29a (n = 1), and also used TAA model mouse (total n = 8) liver samples for microarray analysis. We can get only one gene (PDGF-c) as a target of miR-29a which relate to liver fibrosis and down-regulated more than 1.5 times in common miR-29a injected group than N.C group. CCl4 and TAA liver fibrosis model mouse were used for this experiment. After five weeks liver fibrosis induction period, mouse have been obserbed for one week (1w) or two weeks (2w) and negative control nucleotide (N.C) or miR-29a were injected every 3 days on this period. We used CCl4 1w N.C (n = 1), 1w miR-29a (n = 1), 2w N.C (n = 1), 2w miR-29a (n = 1), and also used TAA model mouse (total n = 8) liver samples for microarray analysis.
2015-03-31 | E-GEOD-67423 | biostudies-arrayexpress