Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1144625 | ENA |
REPOSITORIES: ENA
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Project description:CCL24 is a profibrotic, proinflammatory chemokine expressed in several chronic fibrotic diseases. In the liver, CCL24 plays a role in fibrosis and inflammation and blocking CCL24 led to reduced liver injury in experimental models. We studied the role of CCL24 in primary sclerosing cholangitis (PSC) and evaluated the potential therapeutic effect of blocking CCL24 in this disease. Mdr2-/- mice demonstrated CCL24 expression in liver macrophages and were used as a relevant experimental PSC model. CCL24 neutralizing monoclonal antibody, CM-101, significantly improved inflammation, fibrosis and cholestasis-related markers in the biliary area. Moreover, using spatial transcriptomics we observed reduced proliferation and senescence of cholangiocytes following CCL24 neutralization. Next, we demonstrated that CCL24 expression was elevated under profibrotic conditions in primary human cholangiocytes and macrophages and it induced proliferation of primary human hepatic stellate cells and cholangiocytes, which was attenuated following CCL24 inhibition. Correspondingly, CCL24 was found to be highly expressed in liver biopsies of PSC patients. CCL24 serum levels correlated with Enhanced Liver Fibrosis score, most notably in patients with high alkaline phosphatase levels. These results suggest that blocking CCL24 may have a therapeutic effect in PSC patients via reduced liver inflammation, fibrosis and cholestasis.
2023-04-30 | GSE228596 | GEO
Project description:In this study we performed MeRIP-Seq to study N6-methyl adenosine (m6A) and and N6,2′ -O-dimethyladenosine (m6Am) modification of mRNA. We investigated the effect of the microbiota on the transcriptome and epitranscriptomic modifications in murine liver and cecum. We compared m6A/m modification profiles in cecum of conventionally raised (CONV) and germ-free (GF) mice. We additionally included GF mice colonised with the flora of CONV mice for four weeks (ex-GF), for which show that they exhibit similar patterns of the most abundant genera of gut bacteria as CONV mice. We added mice treated with several antibiotics to deplete the gut flora (abx)and vancomycin treated mice in which the genera Akkermansia, Escherichia/Shigella and Lactobacillus were enriched. Furthermore, we included GF mice colonised with the commensal bacterium Akkermansia muciniphila (Am), Lactobacillus plantarum (Lp) and Escherichia coli Nissle (Ec) and analysed their m6A/m modification profiles. In addition, we analysed changes in m6A/m- modified liver RNA for CONV, GF, and Am, Lp and Ec mice.
2020-02-12 | E-MTAB-6560 | biostudies-arrayexpress
Project description:Regulatory T cells (Tregs) were shown to protect from cholestatic liver injury. Here we investigate whether amphiregulin (AREG), a ligand for epithelial growth factor receptor (EGFR) which promotes epithelial repair, mediates innate Treg functions in cholangiopathies. Mice were fed with diet containing 0.1 % of the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 14 days to induce sclerosing cholangitis, followed by a 28-day recovery period (without DDC). Liver mononuclear and epithelial cells were enriched and subjected to single-cell sequencing at four time points: baseline, at day 14 of DDC treatment, and following a 14- or 28-day recovery period from 14 days of DDC treatment.
2025-12-31 | GSE230091 | GEO
Project description:The potential of orally administered colostrum-derived EVs to regulate gut microbiota dysbiosis and prevent non-alcoholic steatohepatitis was evaluated. The results demonstrated that colostrum-derived EVs improved steatosis, fibrosis, and inflammation. Transcriptome analysis showed decreased lipid metabolism, bacterial response, and inflammatory responses in the intestine, and reduced inflammatory and fibrosis-related pathways in the liver. Gut microbiota and metabolite analysis revealed an increased abundance of Akkermansia and elevated cholesterol excretion. Additionally, treatment with colostrum-derived EVs increased the production of tight junction proteins and mucin in the intestine. These findings suggest that increased Akkermansia due to colostrum-derived EVs improves intestinal inflammation and barrier function, preventing endotoxin translocation to the liver and thereby reducing liver inflammation and fibrosis.
2024-08-01 | GSE273582 | GEO
Project description:Cholangiocarcinoma (CCA) is a dreaded complication of primary sclerosing cholangitis (PSC), difficult to diagnose and associated with high mortality. Lack of animal models of CCA recapitulating the hepatic microenvironment of sclerosing cholangitis hinders development of novel treatments. We have developed and characterized a new mouse model of PSC-CCA through hydrodynamic tail vein injection of oncogenes pT3-EF1a-HA-myrAKT (AKT) and pT3-EF1a-YapS127A (YAP1), termed SB CCA.Mdr2-/-, which features reliable tumor induction in PSC-like background of biliary injury and fibrosis. To unravel the potential molecular profile of CCA developed in different liver context, we profiled the transcriptomes of tumor-bearing fibrotic (Mdr2-/-) (n = 6) and tumor-bearing wild-type liver tissues (n = 6) and compared to corresponding control nontumor-bearing fibrotic (Mdr2-/-) (n = 6) and healthy liver tissues (n = 6). RNA-seq analysis revealed profound transcriptional differences in CCA evolving in PSC-like context, compared to CCA in healthy liver.
2024-06-03 | GSE268905 | GEO
Project description:Regulatory T cells (Tregs) were shown to protect from cholestatic liver injury. Here we investigate whether amphiregulin (AREG), a ligand for epithelial growth factor receptor (EGFR) which promotes epithelial repair, mediates innate Treg functions in cholangiopathies. Mice were fed with diet containing 0.1 % of the xenobiotic 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) for 14 days to induce sclerosing cholangitis, followed by a 28-day recovery period (without DDC). Liver mononuclear and epithelial cells were enriched and subjected to single-cell sequencing at six time points: baseline, at days 7 or 14 of DDC treatment, and following a 7-, 14- or 28-day recovery period from 14 days of DDC treatment.
2025-12-31 | GSE230085 | GEO
Project description:24-Nor-ursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for treating immune-mediated cholestatic liver disease, such as primary sclerosing cholangitis (PSC). Since PSC strongly associates with TH17-mediated tissue inflammation, we explored NorUDCA’s immunomodulatory potential on TH17 cells. Using an unbiased bulk RNA sequencing approach, we discovered that brief exposure (4 hour) to NorUDCA reshapes transcriptomic landscape of murine pathogenic (p)TH17 cells with top enriched pathways of mTORC1 signaling, hypoxia, Myc and associated metabolic processes, such as glycolysis and OXPHOS. NorUDCA treatment also modulates expression of several genes involved in KEGG glutamine pathway, indicating NorUDCA might affect pTH17 cell glutamine metabolism. Taken together, our bulk RNA sequencing data demonstrate NorUDCA’s therapeutic efficacy in modulating pTH17 immunometabolism, potentiating future clinical applications for treating TH17-mediated disease and beyond.
2025-06-30 | GSE285363 | GEO
Project description:Akkermansia muciniphila in the small intestine improves liver fibrosis and hyperammonemia in a murine liver cirrhosis model
| PRJDB17287 | ENA
Project description:Liver array following CMPF treatment
| PRJNA417491 | ENA