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Regional transcriptomics and proteomics of DMPK genes in human intestine

ABSTRACT: Regional transcriptomics and proteomics of DMPK genes in human intestine

PROVIDER: PRJNA889700 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21870349.fastq.gz	Fastqsanger.gz
	SRR21870350.fastq.gz	Fastqsanger.gz
	SRR21870351.fastq.gz	Fastqsanger.gz
	SRR21870352.fastq.gz	Fastqsanger.gz
	SRR21870353.fastq.gz	Fastqsanger.gz

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Regional transcriptomics and proteomics of DMPK genes in human intestine

Project description:The intestine is an organ responsible for absorption and metabolism of orally administered drugs. It is necessary to examine the human intestinal expression profiles of the genes related to drug absorption, distribution, metabolism, and excretion (ADME), for accurate prediction of pharmacokinetics in the intestine. However, previous studies had issues such as the evaluation limited to specific molecules and regions, and relatively small sample sizes. In this study, to obtain more accurate expression profiles of mRNA and protein in various regions of human intestine, biopsy samples were collected from 38 patients with various regions, duodenum, jejunum, ileum, colon and rectum, and RNA-seq analysis and quantitative proteomics analysis were performed. We performed the expression analysis of drug-metabolizing enzymes (cytochromes P450 (CYP ) and non–CYP enzymes), apical and basolateral drug transporters, and nuclear receptors. Overall, mRNA expression levels of these ADME-related molecules were highly correlated with the protein expression levels. The characteristics of the expression of ADME-related genes in human small and large intestines differed significantly, such as higher or lower expression levels of CYP enzymes in the small or large intestines, respectively. Most CYPs were expressed dominantly in the small intestine. Non-CYPs were expressed in the large intestine, but their expression levels were lower than those in the small intestine. The expression levels of ADME-related genes differed even between the proximal and distal small intestine. The expression of transporters showed their highest abundance in the ileum. The data in the present study contributes to an improved understanding of intestinal ADME of drug candidates, and would be useful for drug discovery research.

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