Whole liver RNAseq
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE278821 | GEO | 2025/10/31
REPOSITORIES: GEO
Similar Datasets
Project description:Chronic liver inflammation and fibrosis are central to liver diseases, including the most prevalent metabolic-dysfunction-associated steatohepatitis (MASH), chronic autoimmune liver diseases and liver cancer. However, the mechanism orchestrating the co-occurrence of liver inflammation and fibrosis, both tightly associated with liver diseases, remains elusive. Here, we show that the hepatocyte derived, miR-122 regulates both, liver inflammation and fibrosis, through independent pathways, and that miR-122 is involved in tuning innate and adaptive hepatic immune responses. In parallel, we show that decrease of miR-122 is associated with liver fibrosis in advance or together with liver inflammation. We show that miR-122 regulates liver tolerance, and its absence attenuates bacterial and parasitic infections, and thus functions as a liver immune rheostat. As such, miR-122 presents a therapeutic target.
2025-10-31 | GSE278823 | GEO
Project description:Chronic liver inflammation and fibrosis are central to liver diseases, including the most prevalent metabolic-dysfunction-associated steatohepatitis (MASH), chronic autoimmune liver diseases and liver cancer. However, the mechanism orchestrating the co-occurrence of liver inflammation and fibrosis, both tightly associated with liver diseases, remains elusive. Here, we show that the hepatocyte derived, miR-122 regulates both, liver inflammation and fibrosis, through independent pathways, and that miR-122 is involved in tuning innate and adaptive hepatic immune responses. In parallel, we show that decrease of miR-122 is associated with liver fibrosis in advance or together with liver inflammation. We show that miR-122 regulates liver tolerance, and its absence attenuates bacterial and parasitic infections, and thus functions as a liver immune rheostat. As such, miR-122 presents a therapeutic target.
2025-10-31 | GSE278822 | GEO
Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. We show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation, and reduced hepatic expression of fibrosis- and inflammation-related gene pathways.
2025-04-25 | GSE294630 | GEO
Project description:Recent studies have demonstrated that micro (mi)RNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH) compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO)-AIH-liver-network database. They underwent blood sampling and liver biopsy with inflammation grading and fibrosis staging before receiving treatment. To further confirm the microarray data, circulating expression levels of miR-21 and miR-122 were quantified by real-time quantitative polymerase chain reaction in 46 AIH patients, 40 patients with chronic hepatitis C (CHC), and 15 healthy controls. Consistent with the microarray data, serum levels of miR-21 were significantly elevated in AIH patients compared with CHC patients and healthy controls. miR-21 and miR-122 serum levels correlated with alanine aminotransferase levels. Circulating levels of miR-21 and miR-122 were significantly reduced in AIH patients with liver cirrhosis, and were inversely correlated with increased stages of fibrosis. By contrast, levels of circulating miR-21 showed a significant correlation with the histological grades of inflammation in AIH. We postulate that aberrantly expressed serum miRNAs are potential biomarkers of AIH and could be implicated in AIH pathogenesis. Alternations of miR-21 and miR-122 serum levels could reflect their putative roles in the mediation of inflammatory processes in AIH. Case-control study, steroid treatment
2016-08-01 | E-GEOD-71432 | biostudies-arrayexpress
Project description:Modulation of metabolic, inflammatory, and fibrotic pathways by semaglutide in metabolic dysfunction-associated steatohepatitis Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease strongly associated with cardiometabolic risk factors. Semaglutide, a glucagon-like peptide-1 receptor agonist, improves liver histology in MASH, but the underlying signals and pathways driving semaglutide-induced MASH resolution are not well understood. We show that, in two preclinical MASH models, semaglutide improved histological markers of fibrosis and inflammation, and reduced hepatic expression of fibrosis- and inflammation-related gene pathways.
2025-04-25 | GSE294629 | GEO
Project description:Recent studies have demonstrated that micro (mi)RNA molecules can be detected in the circulation and can serve as potential biomarkers of various diseases. This study used microarray analysis to identify aberrantly expressed circulating miRNAs in patients with type 1 autoimmune hepatitis (AIH) compared with healthy controls. Patients with well-documented and untreated AIH were selected from the National Hospital Organization (NHO)-AIH-liver-network database. They underwent blood sampling and liver biopsy with inflammation grading and fibrosis staging before receiving treatment. To further confirm the microarray data, circulating expression levels of miR-21 and miR-122 were quantified by real-time quantitative polymerase chain reaction in 46 AIH patients, 40 patients with chronic hepatitis C (CHC), and 15 healthy controls. Consistent with the microarray data, serum levels of miR-21 were significantly elevated in AIH patients compared with CHC patients and healthy controls. miR-21 and miR-122 serum levels correlated with alanine aminotransferase levels. Circulating levels of miR-21 and miR-122 were significantly reduced in AIH patients with liver cirrhosis, and were inversely correlated with increased stages of fibrosis. By contrast, levels of circulating miR-21 showed a significant correlation with the histological grades of inflammation in AIH. We postulate that aberrantly expressed serum miRNAs are potential biomarkers of AIH and could be implicated in AIH pathogenesis. Alternations of miR-21 and miR-122 serum levels could reflect their putative roles in the mediation of inflammatory processes in AIH.
2016-08-01 | GSE71432 | GEO
Project description:Hepatic injury is often accompanied by pulmonary inflammation and tissue damage, but the underneath mechanism is not fully elucidated. Here we identify hepatic miR-122 as a culprit of pulmonary inflammation induced by various liver injuries. Analyses of acute and chronic liver injury mouse models confirm that liver dysfunction can cause pulmonary inflammation and tissue damage. Injured livers release large amounts of miR-122 in a microvesicle-independent manner into the circulation compared to normal livers. Circulating miR-122 is then preferentially transported to mouse lungs and taken up by alveolar macrophages, in which it binds toll-like receptor 7 (TLR7) and activates inflammatory responses. Depleting plasma miR-122 largely abolishes liver injury-induced pulmonary inflammation and tissue damage. Furthermore, alveolar macrophage activation by miR-122 is blocked by mutating the TLR7-binding UG-rich sequence on miR-122 or knocking out macrophage TLR7. Our findings reveal a novel causative role of hepatic miR-122 in liver injury-induced pulmonary dysfunction.
2018-12-27 | GSE124360 | GEO
Project description:Background/Aim: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease.
2021-07-15 | GSE179961 | GEO
Project description:Background and Aims: Metabolic dysfunction–associated steatotic liver disease (MASLD) affects a heterogeneous group of patients. Among them, those with a cholestatic profile show worse outcomes. Here, we investigated whether E2F2 is involved in MASLD-associated cholestasis and, if so, the role of miRNAs. Methods: E2f2-knockout (E2f2 AQ5 −/−) and wild-type (WT) mice were fed a cholinedeficient high-fat diet (ChD-HFD) or an HFD after injection of diethylnitrosamine (DEN-HFD) to induce metabolic dysfunction–associated steatohepatitis (MASH). E2F2 was overexpressed in the liver by AAV8. Cholestasis was induced by bile duct ligation or by a 3,5-diethoxycarbonyl-1,4-dihydrocollidine-enriched diet. MicroRNA sequencing was performed. Two biopsy-proven MASLD patient cohorts were used. Results: E2F2 deficiency resulted in increased synthesis and excretion of cholesterol, phosphatidylcholine, and bile acids, reducing their storage in the liver while increasing their presence in feces. This was consistent with increased expression of genes involved in biliary lipid metabolism, reduced inflammation and fibrosis, and the generation of a distinct miRNA profile, thereby preventing MASH. Liver-specific induction of E2F2 in vivo hampered the transcriptional program involved in biliary lipid metabolism and upregulated miR-34a-5p, which was downregulated in E2f2−/− mice. The protective effects observed in E2f2−/− mice were lost when a miR-34a-5p mimic was used. Hepatic miR-34a-5p levels were elevated in patients with advanced fibrosis, inflammation, steatosis score, cholelithiasis, and increased serum bile acids and biliary lipids. E2f2 deficiency conferred protection against cholestatic liver injury. Conclusions: E2F2 deficiency protects against MASH and cholestasis, preventing cholesterol accumulation, fibrosis, and inflammation through modulation ofmiR- 34a-5p. This could provide therapeutic benefits for patients with cholestatic MASH.
2025-08-21 | GSE276277 | GEO
Project description:Gremlin-1 has been implicated in liver fibrosis in metabolic dysfunction-associated steatohepatitis (MASH) via inhibition of bone-morphogenetic protein (BMP) signalling and has thereby been identified as a potential therapeutic target. Using human cirrhotic precision-cut liver slices (PCLS) as an ex vivo model systems of MASH fibrosis, we show that neutralisation of Gremlin-1 activity with monoclonal therapeutic antibodies does not reduce liver inflammation or liver fibrosis. Overall, our findings suggest a redundant role for Gremlin-1 in the pathogenesis of liver fibrosis, which is unamenable to therapeutic targeting.
2024-02-21 | GSE245977 | GEO