title: MicroRNAs as regulators of drug transporters, drug-metabolizing enzymes, and tight junctions: implication for intestinal barrier function.
abstract: Drug transporters, drug-metabolizing enzymes, and tight junctions in the small intestine function as an absorption barrier and sometimes as a facilitator of orally administered drugs. The expression of these proteins often fluctuates and thereby causes individual pharmacokinetic variability. MicroRNAs (miRNAs), which are small non-coding RNAs, have recently emerged as a new class of gene regulator. MiRNAs post-transcriptionally regulate gene expression by binding to target mRNA to suppress its translation or regulate its degradation. They have been shown to be key regulators of proteins associated with pharmacokinetics. Moreover, the role of miRNAs on the expression of some proteins expressed in the small intestine has recently been clarified. In this review, we summarize current knowledge regarding the role of miRNAs in the regulation of drug transporters, drug-metabolizing enzymes, and tight junctions as well as its implication for intestinal barrier function. MiRNAs play vital roles in the differentiation, architecture, and barrier function of intestinal epithelial cells, and directly and/or indirectly regulate the expression and function of proteins associated with drug absorption in intestinal epithelial cells. Moreover, the variation of miRNA expression caused by pathological and physiological conditions as well as genetic factors should affect the expression of these proteins. Therefore, miRNAs could be significant factors affecting inter- and intra-individual variations in the pharmacokinetics and intestinal absorption of drugs. Overall, miRNAs could be promising targets for personalized pharmacotherapy or other attractive therapies through intestinal absorption of drugs.
authors.affiliation: Department of Pharmacy, Mie University Hospital, Tsu, Mie 514-8507, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Ikemura
authors.affiliation: Department of Pharmacy, Mie University Hospital, Tsu, Mie 514-8507, Japan; Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iwamoto
authors.affiliation: Department of Pharmacy, Mie University Hospital, Tsu, Mie 514-8507, Japan; Department of Clinical Pharmacy and Biopharmaceutics, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan. Electronic address: okudam@clin.medic.mie-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okuda
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis; D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000096:biosynthesis*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology; D035683:MicroRNAs / Q000378:metabolism*; D010599:Pharmacokinetics; D019108:Tight Junctions / Q000502:physiology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D002352:Carrier Proteins; D035683:MicroRNAs; D003577:Cytochrome P-450 Enzyme System
keywords: Intestinal barrier; Metabolizing enzymes; MicroRNA; Small intestine; Tight junction; Transporter