Peritoneal macrophage heterogeneity in decompensated liver cirrhosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE124878 | GEO | 2020/03/24
REPOSITORIES: GEO
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Project description:Peritoneal macrophage heterogeneity in decompensated liver cirrhosis
| PRJNA514059 | ENA
Project description:Objectives Non-invasive staging of decompensated cirrhosis is an unmeet clinical need. The aims of this study were to characterize and validate a novel miRNA signature to stage decompensated cirrhosis and predict the portal pressure and cardiac dysfunction response to non-selective beta-blockers (NSBB). Design Serum samples from patients with decompensated cirrhosis (n=36) and healthy controls (n=36) were tested for a novel signature of five miRNAs (miR-452-5p, miR-429, miR-885-5p, miR-181b-5p, and miR-122-5p) identified in the secretome of primary human hepatocytes, and three miRNAs (miR-192-5p, miR-34a-5p and miR-29a-5p) previously discovered as biomarkers of chronic liver disease. All patients had ascites, that was refractory in 18 (50%), and were placed on NSBB for variceal bleeding prophylaxis. In all patients, serum miRNAs, hepatic venous pressure gradient (HVPG), and echocardiogram study was performed before and 1 month after NSBB. Results Cirrhotic patients had lower serum levels of miR-429, miR-885-5p, miR-181b-5p, miR-122-5p, miR-192-5p and miR-29a-5p (p<0.05). miR-452-5p and miR-429 expression were lower in NSBB responders (p=0.006). miR-181b-5p expression was greater in refractory- than in diuretic sensitive ascites (p=0.008) and correlated with serum creatinine. miR-452-5p and miR-885-5p were inversely correlated with baseline systemic vascular resistance (ρ=-0.46 p=0.007; and ρ=-0.41 p=0.01 respectively), and with diminished systolic contractility in patients with refractory ascites after NSBB (ρ=-0.55 p=0.02; and ρ=-0.55 p=0.02, respectively). Conclusion Analysis of a miRNA signature in serum distinguishes patients with decompensated cirrhosis who show more severe systemic circulatory dysfunction and compromised systolic function after beta-blockade, and those more likely to benefit from NSBB.
2021-02-10 | GSE150867 | GEO
Project description:MOLECULAR PROFILING OF DECOMPENSATED CIRRHOSIS BY A NOVEL microRNA SIGNATURE
| PRJNA633887 | ENA
Project description:Human serum albumin (HSA) is an emerging treatment for preventing excessive systemic inflammation and organ failure(s) in patients with acutely decompensated (AD) cirrhosis. Here, we investigated the molecular mechanisms underlying the immunomodulatory properties of HSA. Administration of HSA to patients with AD cirrhosis with elevated circulating bacterial DNA (CpG-DNA) was associated with reduced plasma cytokine levels. In isolated leukocytes, HSA abolished CpG-DNA-induced cytokine expression and release independently of its oncotic and scavenging properties. Similar anti-inflammatory effects were observed with recombinant human albumin. HSA exerted widespread changes on the immune cell transcriptome, specifically in genes related to the endosomal compartment involved in cytosolic DNA sensing and type I interferon responses. Flow cytometry and confocal microscopy analyses revealed that HSA was taken up by leukocytes and internalized in vesicles positively stained with EEA1, a marker of early endosomes. Indeed, HSA and CpG-DNA colocalized in endosomes, the compartment where CpG-DNA binds to TLR9, its cognate receptor. Furthermore, HSA also inhibited poly-(I:C)- and LPS-induced IRF3 phosphorylation and TRIF-mediated responses, which are exclusive of endosomal TLR3 and TLR4 signaling, respectively. The immunomodulatory actions of HSA did not compromise leukocyte defensive mechanisms such as phagocytosis, efferocytosis and intracellular ROS production. The in vitro immunomodulatory effects of HSA were confirmed in vivo in analbuminemic humanized FcRn transgenic mice. In conclusion, these findings indicate that HSA internalizes in immune cells and modulates their responses through interaction with endosomal TLR signaling, thus providing a mechanism for the benefits of HSA infusions in patients with cirrhosis.
2023-03-02 | GSE146462 | GEO
Project description:Infections are an important cause of morbidity and mortality in patients with decompensated cirrhosis and ascites. Hypothesising that innate immune dysfunction contributes to susceptibility to infection, we assessed ascitic fluid macrophage phenotype and function. The expression of complement receptor of the immunoglobulin superfamily (CRIg) and CCR2 defined two phenotypically and functionally distinct peritoneal macrophage sub-populations. The proportion of CRIgHi macrophages differed between patients, and in the same patient over time, and a high proportion of CRIgHi macrophages was associated with reduced disease severity (Model for End Stage Liver Disease (MELD)) score. As compared to CRIgLow macrophages, CRIgHi macrophages were highly phagocytic and displayed enhanced antimicrobial effector activity. Transcriptional profiling by RNA Sequencing and comparison with human macrophage and murine peritoneal macrophage expression signatures highlighted similarities between CRIgHi cells, human macrophages and mouse F4/80Hi resident peritoneal macrophages, and between CRIgLow macrophages, human monocytes and mouse F4/80Low monocyte-derived peritoneal macrophages. These data suggest CRIgHi and CRIgLow macrophages may represent a tissue-resident population and a monocyte-derived population, respectively. In conclusion, ascites fluid macrophage subset distribution and phagocytic capacity is highly variable between patients with chronic liver disease. Regulating the numbers and/or functions of these macrophage populations could provide therapeutic opportunities in cirrhotic patients.
2017-08-22 | GSE79833 | GEO
Project description:Background and aims: Patients with decompensated cirrhosis present serious infections of bacterial origin. During homeostasis, resident macrophages from the liver or Kupffer cells (KCS) play a key role in the phagocytosis of circulating bacteria. The objective of this study was to characterize the transcripomic and functional profile of KCs in liver cirrhosis and its relationship with the risk of infections. Methods: KCs were isolated from livers of patients with cirrhosis (n = 4) and controls (n = 5) and the profile was determined by RNA sequencing. The phenotype and altered molecular pathways of the isolated KCS were analyzed through GSEA . Results: The expression profile of KCs is specific and different depending on whether they reside in a cirrhotic or control liver. The GO analysis revealed that the pathways differentially expressed in KCs isolated from cirrhotic liver are implicated in the immune response. The GSEA showed that KCs isolated from patients with cirrhosis present a greater overexpression of M1 markers with respect to M2 (normalized enrichment score, NES: 1.68, p <0.01 vs. NES: 0.8, p <0.01). Conclusion: The KCS of patients with cirrhosis have a unique and distinct gene expression profile characterized by up-regulation of M1 markers.
2020-09-11 | GSE123661 | GEO
Project description:Gene profiling of hepatocytes in early and advanced cirrhotic Rats Two-condition experiment, Advanced cirrhosis vs Control liver, Advanced cirrhosis vs Early cirrhosis. Biological replicates: 5 Advanced cirrhosis, 5 Early cirrhosis, 5 control liver. Each hepatocyte was isolated independently. One replicate per array.
2011-11-02 | E-GEOD-22977 | biostudies-arrayexpress
Project description:Purpose: Characterize the gene expression profile of wild-type and Zeb1 (+/-) peritoneal mouse macrophages through RNA sequencing Methods: RNA sequencing of RNA from peritoneal macrophages isolated by peritoneal lavage and FACS sorting (F4/80+ CD11b+) from wild-type and Zeb1 (+/-) mice (2 mice pooled for each sample/set) Results: Wild-type and Zeb1 (+/-) peritoneal mouse macrophages display differential gene expression. Zeb1 (+/-) peritoneal macrophages express lower levels of SPM (F4/80low)-associated genes Conclusions: Wild-type and Zeb1 (+/-) peritoneal mouse macrophages display differential gene expression. Zeb1 (+/-) peritoneal macrophages express lower levels of SPM (F4/80low)-associated genes
2019-05-24 | GSE103830 | GEO
Project description:Cirrhosis, advanced liver disease, affects 2-5 million Americans. While most patients have compensated cirrhosis and may be fairly asymptomatic, many decompensate and experience life-threatening complications such as gastrointestinal bleeding, confusion (hepatic encephalopathy), and ascites, reducing life expectancy from 12 to less than 2 years. Among the patients with compensated cirrhosis, identifying patients at high risk of decompensation is critical to optimize care, reduce morbidity and mortality. This is important to preferentially direct them towards specialty care which cannot be provided to all patients with cirrhosis. We used discovery Top-down Proteomics (TDP) to detect differentially expressed proteoforms (DEPs) in the plasma of patients with cirrhosis with the goal to identify candidate biomarkers of disease progression. 663 DEPs were identified across three stages of cirrhosis (compensated, compensated with portal hypertension, and decompensated), of which 115 derived from proteins enriched in the liver at a transcriptional level and discriminated the progressive stages of cirrhosis. Enrichment analyses demonstrated DEPs are involved in numerous metabolic, oxidative, immunological, and hematological processes known to be impacted by cirrhosis progression. We have preliminarily defined the plasma proteoform signatures of cirrhosis patients, setting the stage for ongoing discovery and validation of biomarkers for early diagnosis, risk stratification, and disease monitoring.
2024-03-13 | MSV000094311 | MassIVE
Project description:Cirrhosis and cancers of the upper digestive tract, colorectal and ENT share common risk factors. Liver cirrhosis can change the elimination of cancer drugs.
Precise data on management and outcome of patients with liver cirrhosis undergoing chemotherapy are lacking. Most patients have been excluded from clinical trials evaluating conventional therapies.
The study of tolerance, side effects, and outcome in patients with cirrhosis could help improve chemotherapy management for better tolerance and efficacy.
The main objective is to estimate the frequency of liver cirrhosis among patients evaluated in CPR for ENT, upper digestive or colorectal cancer.
Secondary objective includes the evaluation ofthe impact of cirrhosis on the management of chemotherapy by comparing cirrhotic patients’ outcomes with a control group of matched non-cirrhotic patients.
| 2323209 | ecrin-mdr-crc