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A time-course study of thioacetamide (TAA)-induced liver fibrosis in rats

ABSTRACT: A time-course study of thioacetamide (TAA)-induced liver fibrosis in rats

PROVIDER: PRJEB45544 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR6016480.fastq.gz	Fastqsanger.gz
	ERR6016490.fastq.gz	Fastqsanger.gz
	ERR6016500.fastq.gz	Fastqsanger.gz
	ERR6016510.fastq.gz	Fastqsanger.gz
	ERR6016481.fastq.gz	Fastqsanger.gz

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A time-course study of thioacetamide (TAA)-induced liver fibrosis in rats

Project description:The aim is to characterize rat liver fibrosis induced by thioacetamide (TAA). To induce hepatic fibrosis, Male Sprague Dawley rats (9-12 weeks of age and 380-420 g of weight upon arrival, supplied by Beijing Vital River laboratory animal Co., Ltd.) were treated with thioacetamide (TAA). Rat liver samples were collected from five groups of rats at week 1, 2, 4, 8 and 13 after TAA (300 mg/kg) administration three times per week while five control groups receive the same volume of 0.9% normal saline. Four biological replicates were used for each group.

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Transcriptomic profile of zebrafish liver cells in thioacetamide (TAA) model

Project description:Zebrafish transgenic lines Tg(fabp10a:dsRed), Tg(hand2:EGFP) and Tg(kdrl:ras-mCherry) in AB wild-type background were anesthetized with MS-222 and adult females were injected intraperitoneally with 500 mg/kg thioacetamide (TAA) or sterile water as a control 6 times over the course of 2 weeks. We have characterized transcriptomic profiles of FACS-isolated hepatocytes (dsRed+), stellate cells (EGFP+) and liver endothelial cells (mCherry+) from fishes treated with TAA or sterile water. Cells negative for the fluorescence were used as a control.

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Project description:Zebrafish transgenic lines Tg(fabp10a:dsRed), Tg(hand2:EGFP) and Tg(kdrl:ras-mCherry) in AB wild-type background were anesthetized with MS-222 and adult females were injected intraperitoneally with 500 mg/kg thioacetamide (TAA) or sterile water as a control 6 times over the course of 2 weeks. We have characterized chromatin accessibility profiles of FACS-isolated hepatocytes (dsRed+), stellate cells (EGFP+) and liver endothelial cells (mCherry+) from fishes treated with TAA or sterile water. Cells negative for the fluorescence were used as a control.

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Project description:Metabolomic analysis on hepatic stellate cells isolated from PBS- or thioacetamide (TAA)-treated wild-type and Cyp1b1 knockout mice was performed to determine the metabolic basis by which CYP1B1 ablation inhibits HSC activation and liver fibrosis.

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Mechanistic roles of microRNAs in hepatocarcinogenesis: A study of thioacetamide with multiple doses and time-points of rats

Project description:Environmental chemicals exposure are one of the primary factors for liver toxicity and hepatocarcinoma. Thioacetamide (TAA) is a well-known hepatotoxicant and could be a liver carcinogen in humans.The discovery of early and sensitive biomarkers in liver injury and tumor progression could improve cancer diagnosis, prognosis, and management. In the present study, we studied the dynamic changes in microRNAs (miRNAs) expression and explored the potential mechanistic role of miRNAs in rat liver treated with TAA at multiple doses and time points. Sprague-Dawley rats were administrated with TAA at three doses [low (4.5 mg/kg), middle (15mg/kg) and high (45mg/kg)] and four repeated treatment durations (3-, 7-, 14- and 28-days). Expressions of miRNAs in livers were profiled using next generation sequencing and analyzed. Overall, 330 unique differentially expressed miRNAs (DEMs) were identified in the entire TAA-treatment course. Of these, 129 DEMs were found significantly enriched for the “liver cancer” annotation. These results were further complemented by pathway analysis in which “Molecular Mechanisms of Cancer”, “p53-”, “TGF-β-”, “MAPK-” and “Wnt-signaling” were significantly enriched in most TAA-treatment conditions. Two miRNAs (rno-miR-34a-5p and rno-miR-455-3p) out of 48 DEMs (common across all the treatment conditions) were identified to be early and sensitive biomarkers for TAA-induced hepatocarcinogenicity. Upregulation of rno-miR-34a-5p was further confirmed by qPCR. These findings reveal the critical role of miRNAs in the mechanisms underlying hepatocarcinogenesis and potential application for human risk assessment. Most importantly, rno-miR-34a-5p is the most suitable early and sensitive biomarker for TAA-induced hepatocarcinogenesis due to its consistent elevation during the entire treatment course.

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Project description:Aims: We sought to discover the effect of celecoxib on thioacetamide-induced liver fibrosis in mice with single cell RNA sequencing (scRNA-seq). Methods: A fibrotic mouse model was established by intraperitoneal injection of thioacetamide, and celecoxib was used as the treatment. Mice livers were collected and analyzed with scENA-seq. Results: scRNA-seq revealed prominent transcriptomic changes especially in B cells in liver fibrosis and after celecoxib treatment. KEGG pathways of the B-cell receptor signaling pathway and antigen processing and presentation were enriched, and the gene expression of receptors such as CXCR4 was altered. Conclusions: Celecoxib might modulate intrahepatic B cells to ameliorate liver fibrosis.

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