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dc.contributor.authorBeaudoin, James
dc.contributor.authorBrouwer, Kim
dc.contributor.authorMalinen, Melina
dc.date.accessioned2020-09-21T10:58:04Z
dc.date.available2020-09-21T10:58:04Z
dc.date.issued2020
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/8321
dc.description.abstractOrganic solute transporter alpha/beta (OSTα/β) is a heteromeric solute carrier protein that transports bile acids, steroid metabolites and drugs into and out of cells. OSTα/β protein is expressed in various tissues, but its expression is highest in the gastrointestinal tract where it facilitates the recirculation of bile acids from the gut to the liver. Previous studies established that OSTα/β is upregulated in liver tissue of patients with extrahepatic cholestasis, obstructive cholestasis, and primary biliary cholangitis (PBC), conditions that are characterized by elevated bile acid concentrations in the liver and/or systemic circulation. The discovery that OSTα/β is highly upregulated in the liver of patients with nonalcoholic steatohepatitis (NASH) further highlights the clinical relevance of this transporter because the incidence of NASH is increasing at an alarming rate with the obesity epidemic. Since OSTα/β is closely linked to the homeostasis of bile acids, and tightly regulated by the nuclear receptor farnesoid X receptor, OSTα/β is a potential drug target for treatment of cholestatic liver disease, and other bile acid-related metabolic disorders such as obesity and diabetes. Obeticholic acid, a semi-synthetic bile acid used to treat PBC, under review for the treatment of NASH, and in development for the treatment of other metabolic disorders, induces OSTα/β. Some drugs associated with hepatotoxicity inhibit OSTα/β, suggesting a possible role for OSTα/β in drug-induced liver injury (DILI). Furthermore, clinical cases of homozygous genetic defects in both OSTα/β subunits resulting in diarrhea and features of cholestasis have been reported. This review article has been compiled to comprehensively summarize the recent data emerging on OSTα/β, recapitulating the available literature on the structure-function and expression-function relationships of OSTα/β, the regulation of this important transporter, the interaction of drugs and other compounds with OSTα/β, and the comparison of OSTα/β with other solute carrier transporters as well as adenosine triphosphate-binding cassette transporters. Findings from basic to more clinically focused research efforts are described and discussed.
dc.language.isoenglanti
dc.publisherElsevier BV
dc.relation.ispartofseriesPharmacology and therapeutics
dc.relation.urihttp://dx.doi.org/10.1016/j.pharmthera.2020.107542
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectbile acids
dc.subjectcholestasis
dc.subjectdrug interactions
dc.subjectgenetic variation
dc.subjectNASH
dc.subjectSLC51
dc.titleNovel Insights into the Organic Solute Transporter Alpha/Beta, OSTα/β: From the Bench to the Bedside
dc.description.versionpublished version
dc.contributor.departmentSchool of Pharmacy, Activities
uef.solecris.id69807468en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© 2020 The Authors
dc.relation.doi10.1016/j.pharmthera.2020.107542
dc.description.reviewstatuspeerReviewed
dc.relation.articlenumber107542
dc.relation.issn0163-7258
dc.relation.volume211
dc.rights.accesslevelopenAccess
dc.type.okmA2
uef.solecris.openaccessHybridijulkaisukanavassa ilmestynyt avoin julkaisu


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