Organic 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.

中文翻译：

---

对有机溶质转运蛋白 α/β、OSTα/β 的新见解：从实验室到床边。


有机溶质转运蛋白 α/β (OSTα/β) 是一种异聚溶质载体蛋白，可将胆汁酸、类固醇代谢物和药物转运进出细胞。 OSTα/β蛋白在多种组织中表达，但其表达在胃肠道中最高，它促进胆汁酸从肠道到肝脏的再循环。先前的研究表明，肝外胆汁淤积、阻塞性胆汁淤积和原发性胆汁性胆管炎 (PBC) 患者的肝组织中 OSTα/β 表达上调，这些疾病的特征是肝脏和/或体循环中胆汁酸浓度升高。 OSTα/β 在非酒精性脂肪性肝炎 (NASH) 患者肝脏中高度上调的发现进一步凸显了这种转运蛋白的临床相关性，因为随着肥胖的流行，NASH 的发病率正在以惊人的速度增加。由于 OSTα/β 与胆汁酸的稳态密切相关，并受到核受体法尼醇 X 受体的严格调节，因此 OSTα/β 是治疗胆汁淤积性肝病和其他胆汁酸相关代谢性疾病（例如肥胖和糖尿病。奥贝胆酸是一种用于治疗 PBC 的半合成胆汁酸，目前正在审查用于治疗 NASH 的情况，并正在开发用于治疗其他代谢性疾病的方法，它会诱导 OSTα/β。一些与肝毒性相关的药物会抑制 OSTα/β，表明 OSTα/β 在药物性肝损伤 (DILI) 中可能发挥作用。此外，OSTα/β 亚基纯合性遗传缺陷导致腹泻和胆汁淤积特征的临床病例已有报道。 这篇综述文章全面总结了 OSTα/β 的最新数据，概括了有关 OSTα/β 的结构-功能和表达-功能关系、这一重要转运蛋白的调节、药物相互作用和其他方面的现有文献。 OSTα/β 化合物，以及 OSTα/β 与其他溶质载体转运蛋白以及三磷酸腺苷结合盒转运蛋白的比较。描述和讨论了从基础研究到更注重临床的研究工作的结果。