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ABSTRACT: Human ileum samples

PROVIDER: PRJNA610930 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11276700_1.fastq.gz	Fastqsanger.gz
	SRR11276700_2.fastq.gz	Fastqsanger.gz
	SRR11276701_1.fastq.gz	Fastqsanger.gz
	SRR11276701_2.fastq.gz	Fastqsanger.gz
	SRR11276702_1.fastq.gz	Fastqsanger.gz

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Project description:Orally administered drugs are absorbed and metabolized in the intestine. In order to accurately predict pharmacokinetics in the intestine, it is essential to understand the intestinal expression profiles of genes related to drug absorption, distribution, metabolism, and excretion (ADME). However, in many previous studies, gene expression analysis in the intestine has been carried out using specimens from cancer patients. In this study, in order to obtain a more accurate gene expression profile, biopsy samples were collected from 14 patients under endoscopic observation and RNA-seq analysis was performed. Gene expression analysis of drug metabolizing enzymes (CYPs), non-CYP enzymes, nuclear receptors, drug conjugating enzymes (UGTs and SULTs), and apical and basolateral drug transporters was performed in biopsy samples from the duodenum, ileum, colon, and rectum. The proportions of the CYPs expressed in the ileum were 25% (CYP3A4), 19% (CYP2C18), and 14% (CYP3A5). CYP3A4 and CYP2C19 were highly expressed in the duodenum and ileum, but not in the colon and rectum. In the ileum, apical transporters such as P-gp, PEPT1, BCRP, MRP2, and ASBT were strongly expressed, and the expression levels of P-gp and ASBT in the ileum were higher than those in other regions. In the ileum, basolateral transporters such as OSTα, OSTβ, and MRP3 were strongly expressed. Furthermore, we identified specific markers for the duodenum, ileum, colon, and rectum by conducting comprehensive gene expression analysis. We succeeded in obtaining gene expression profiles of drug ADME-related genes in vivo human intestinal epithelial cells. We expect that this information would be useful for accurate prediction of the pharmacokinetics of oral drugs.

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