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RNA-seq of precision cut liver slice (PCLS) culture before slicing and up to nine days after slicing

ABSTRACT: RNA-seq of precision cut liver slice (PCLS) culture before slicing and up to nine days after slicing

PROVIDER: PRJEB29531 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR2869090.fastq.gz	Fastqsanger.gz
	ERR2869100.fastq.gz	Fastqsanger.gz
	ERR2869110.fastq.gz	Fastqsanger.gz
	ERR2869120.fastq.gz	Fastqsanger.gz
	ERR2869130.fastq.gz	Fastqsanger.gz

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RNA-seq of precision cut liver slice (PCLS) culture before slicing and up to nine days after slicing

Project description:The purpose of this experiment is to test the effect of culture time and on liver slices. We generated liver slices from saltwater-stage Atlantic salmon and cultured them over a period of nine days. Samples were taken before slicing and 1, 3, 4, 5, 6, 7, 8, and 9 days after slicing. After three days, half of the samples were treated with alpha-linolenic acid (ALA) complexed with methyl-beta cyclodextrin (BCD) and the rest received a control treatment of empty BCD.

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RNA-seq of precision cut liver slice (PCLS) culture before slicing and up to 9 days after slicing, changing media either every day or every 3 days, with insulin

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Project description:Precision-cut liver tissue slice (PCLS) contains all major cell types of the liver parenchyma and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study liver fibrosis and test the anti-fibrotic effect of experimental compounds in a physiologic environment. In this study using RNAquencing we demonstrated that various pathways functionally related to fibrotic mechanisms were dysregulated in PCLSs derived from rats subjected to bile duct ligation. The Alk5 inhibitor SB525334, nintedanib and sorafenib each reversed a subset of genes dysregulated in fibrotic PCLSs and of those genes we identified 608 genes whose expression was reversed by all three compounds. These genes define a molecular signature characterizing many aspects of liver fibrosis pathology and its attenuation in the model. A panel of 12 genes and 4 secreted biomarkers including procollagen I, HA, IGFBP5 and WISP1, were further validated as efficacy endpoints for the evaluation of anti-fibrotic activity of experimental compounds. Finally, we showed that blockade of αV integrins with a small molecule inhibitor attenuated the fibrotic phenotype in the model. Overall, our results suggest that the rat fibrotic PCLS model may represent a valuable system for target validation and to determine the efficacy of experimental compounds.

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