Liver isolated single cell RNAseq v1
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE278822 | GEO | 2025/10/31
REPOSITORIES: GEO
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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 | GSE278821 | 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 | GSE278823 | 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: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:The liver-specific microRNA, miR-122, is an essential host factor for replication of hepatitis C virus (HCV), an important infectious cause of chronic liver disease and hepatocellular carcinoma. miR-122 stabilizes the positive-strand HCV RNA genome and promotes viral RNA synthesis by binding two closely spaced sites (S1 and S2) near the 5’ end of the genome in association with Ago2. Ago2 is essential for both host factor activities, but whether other host proteins are involved is unknown. Using a quantitative proteomics approach, we identified TNRC6A (GW182) and its paralogs (TNRC6B and TNRC6C), as functionally important components of the miR-122/Ago2 host factor complex binding HCV RNA. Depletion of any two TNRC6 proteins reduced HCV replication in Huh-7.5 cells,but did not reduce viral RNA stability or translational activity, but rather dampened miR-122 stimulation of viral RNA synthesis. However, TNRC6 depletion had no effect on replication of HCV in which S2 was mutated so that miR-122 binds only S1, whereas it significantly enhanced replication when S1 was mutated and only S2 bound by miR-122. Consistent with this, we found that TNRC6 proteins preferentially associate with the S1 site, and that the association of Ago2 with S2 is increased in TNRC6-depleted cells. Collectively, these data suggest a model in which TNRC6 proteins, which are known to interact with Ago2, preferentially direct the miR-122/Ago2 complex to S1 while restricting its association with S2, thereby fine tuning the spatial organization of miR-122/Ago2 complexes bound to the viral RNA.
2019-04-24 | PXD013054 | Pride
Project description:Renal interstitial fibrosis (RIF) is a common pathological feature and final manifestation of chronic progressive kidney disease. Although exosome-mediated intercellular communication is known to play a crucial role in RIF, the mechanism by which injured tubular epithelial cells (TECs) contribute to fibrogenesis remains incompletely understood. In this study, we investigated the role of exosomal miR-122-5p derived from TECs in modulating fibroblast activation and renal fibrosis. Exosomes were isolated from kidneys of unilateral ureteral obstruction (UUO) mice and from TGF-β1-stimulated HK-2 cells. These exosomes were either co-cultured with fibroblasts (NRK-49F cells) or injected into UUO mice via the tail vein. High-throughput miRNA profiling was used to identify differentially expressed miRNAs in exosomes derived from HK-2 cells, and miR-122-5p was selected for further investigation based on expression level and bioinformatic prediction. Functional analyses were performed using miRNA mimics, inhibitors, and target validation assays. The results showed that exosomal miR-122-5p was significantly downregulated in both fibrotic kidneys and TGF-β1-induced HK-2 cells. In vivo and in vitro, restoration of miR-122-5p levels markedly attenuated renal fibrosis, as evidenced by the reduction of fibrotic markers including α-smooth muscle actin, fibronectin, and collagen I. Mechanistically, miR-122-5p was found to directly target hypoxia-inducible factor 1-alpha (HIF-1α), thereby inhibiting activation of the TGF-β1/Smad signaling pathway. These findings suggest that decreased expression of miR-122-5p in TEC-derived exosomes promotes renal fibrosis through the HIF-1α/TGF-β1/Smad axis, while reintroduction of miR-122-5p can effectively reverse these effects. Taken together, our study provides new insights into the intercellular communication between TECs and fibroblasts via exosomal miRNAs, and identifies miR-122-5p as a potential therapeutic target for the treatment of renal interstitial fibrosis.
2025-09-19 | GSE305699 | GEO
Project description:MicroRNA-122, an abundant and conserved liver-specific miRNA, regulates hepatic metabolism and functions as a tumor suppressor, yet systematic and direct biochemical elucidation of the miR-122 target network remains incomplete. To this end, we performed Argonaute crosslinking immunoprecipitation (Ago-CLIP) sequencing in miR-122 knockout and control mouse livers, as well as in matched human hepatocellular carcinoma (HCC) and benign liver tissue to identify miRNA target sites transcriptome-wide in two species. We observed a majority of miR-122 binding on 3’-UTRs and coding exons followed by extensive binding to other genic and non-genic sites. Motif analysis of miR-122 dependent binding revealed a novel G-bulged motif in addition to canonical motifs. A large number of miR-122 targets were found to be species-specific. Upregulation of several common mouse and human targets, most notably BCL9, predicted survival in HCC patients. These results broadly define the molecular consequences of miR-122 downregulation in hepatocellular carcinoma.
2017-03-28 | GSE97060 | GEO