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Gene expression profile at single cell level of non-parenchymal cells from Fibrosis and Tumor (FAT) Metabolic Dysfunction-Associated Steatohepatitis (MASH) model vs healthy liver at 12- and 24-week timepoints.

ABSTRACT: Gene expression profile at single cell level of non-parenchymal cells from Fibrosis and Tumor (FAT) Metabolic Dysfunction-Associated Steatohepatitis (MASH) model vs healthy liver at 12- and 24-week timepoints.

PROVIDER: PRJNA1085495 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28259581.fastq.gz	Fastqsanger.gz
	SRR28259582.fastq.gz	Fastqsanger.gz
	SRR28259583.fastq.gz	Fastqsanger.gz
	SRR28259584.fastq.gz	Fastqsanger.gz
	SRR28259585.fastq.gz	Fastqsanger.gz

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Gene expression profile at single cell level of non-parenchymal cells from Fibrosis and Tumor (FAT) Metabolic Dysfunction-Associated Steatohepatitis (MASH) model vs healthy liver at 12- and 24-week timepoints.

Project description:MASH is a subtype of metabolic dysfunction-associated steatotic liver disease, characterized by inflammation and fibrosis. Non-parenchymal cells in this dataset include mostly immune cells, as well as some other cell types like endothelial cells, cholangiocytes, stellate cells, etc.

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Serum Protein Risk Stratification Score for Diagnostic Evaluation of Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Project description:Reliable non-invasive tools to diagnose at risk metabolic dysfunction-associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high risk MASH patients (NAFLD Activity Score (NAS) >4 and fibrosis score >2). In this three-phase proteomic study of biopsy-proven metabolic dysfunction-associated steatotic fatty liver disease (MASLD), we first developed a multi-protein predictor for discriminating NAS>4 based on SOMAscan proteomics quantifying 1,305 serum proteins from 57 US patients. Four key predictor proteins were verified by ELISA in the expanded US cohort (N=168), and enhanced by adding clinical variables to create the 9-feature MASH Dx Score which predicted MASH and also high risk MASH (F2+). The MASH Dx Score was validated in two independent, external cohorts from Germany (N=139) and Brazil (N=177). The discovery phase identified a 6-protein classifier that achieved an AUC of 0.93 for identifying MASH. Significant elevation of four proteins (THBS2, GDF15, SELE, IGFBP7) was verified by ELISA in the expanded discovery and independently in the two external cohorts. MASH Dx Score incorporated these proteins with established MASH risk factors (age, BMI, ALT, diabetes, hypertension) to achieve good discrimination between MASH and MASLD without MASH (AUC:0.87- discovery; 0.83- pooled external validation cohorts), with similar performance when evaluating high risk MASH F2-4 (vs. MASH F0-1 and MASLD without MASH). The MASH Dx Score offers the first reliable non-invasive approach combining novel, biologically plausible ELISA-based fibrosis markers and clinical parameters to detect high risk MASH in patient cohorts from the US, Brasil and Europe.

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Effects of engineered IL-18BP on attenuation of MASH liver

Project description:Metabolic dysfunction-associated steatohepatitis (MASH) is a chronic liver disease associated with hepatic inflammation and fibrosis. Inflammasome-mediated IL-18 signaling is enhanced under MASH condition. IL-18 binding protein (IL-18BP) is a soluble protein that can block IL-18 actions and therapeutic potential of IL-18BP for MASH-induced fibrosis is largely unknown. We newly developed a human IL-18BP biologics (APB-R3) and injected it to mice to evaluate its pharmacologic efficacy. APB-R3 strikingly abolished hepatic fibrosis and reduced collagen markers. We further investigated whether APB-R3 could inhibit fibrotic activation of hepatic stellate cells (HSCs). This study proposes that abrogation of IL-18 signaling by boosting IL-18BP can strongly inhibit the development of MASH-induced fibrosis and our engineered IL-18BP biologics can become promising therapeutic candidate for curing MASH.

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