The Na ( +)-taurocholate cotransporting polypeptide (NTCP) is a member of the solute carrier family 10 (SLC10), which consists of 7 members (SLC10a1-SLC10a7). NTCP is a transporter localized to the basolateral membrane of hepatocytes and is primarily responsible for the absorption of bile acids. Although mammalian NTCP has been extensively studied, little is known about the lamprey NTCP (L-NTCP). Here we show that L-NTCP follows the biological evolutionary history of vertebrates, with conserved domain, motif, and similar tertiary structure to higher vertebrates. L-NTCP is localized to the cell surface of lamprey primary hepatocytes by immunofluorescence analysis. HepG2 cells overexpressing L-NTCP also showed the distribution of L-NTCP on the cell surface. The expression profile of L-NTCP showed that the expression of NTCP is highest in lamprey liver tissue. L-NTCP also has the ability to transport bile acids, consistent with its higher vertebrate orthologs. Finally, using a farnesoid X receptor (FXR) antagonist, RT-qPCR and flow cytometry results showed that L-NTCP is negatively regulated by the nuclear receptor FXR. This study is important for understanding the adaptive mechanisms of bile acid metabolism after lamprey biliary atresia based on understanding the origin, evolution, expression profile, biological function, and expression regulation of L-NTCP.

Na (+)-牛磺胆酸盐共转运多肽 (NTCP) 是溶质载体家族 10 (SLC10) 的成员，该家族由 7 个成员 (SLC10a1-SLC10a7) 组成。 NTCP 是一种位于肝细胞基底外侧膜的转运蛋白，主要负责胆汁酸的吸收。尽管哺乳动物 NTCP 已被广泛研究，但对七鳃鳗 NTCP (L-NTCP) 知之甚少。在这里，我们证明L-NTCP遵循脊椎动物的生物进化史，具有保守的结构域、基序和与高等脊椎动物相似的三级结构。通过免疫荧光分析，L-NTCP 定位于七鳃鳗原代肝细胞的细胞表面。过表达L-NTCP的HepG2细胞也显示出L-NTCP在细胞表面的分布。 L-NTCP的表达谱显示，NTCP在七鳃鳗肝组织中的表达量最高。 L-NTCP 还具有运输胆汁酸的能力，与其高等脊椎动物的直系同源物一致。最后，使用法尼醇X受体（FXR）拮抗剂，RT-qPCR和流式细胞术结果表明L-NTCP受到核受体FXR的负向调节。本研究在了解L-NTCP的起源、进化、表达谱、生物学功能和表达调控的基础上，对于了解七鳃鳗胆道闭锁后胆汁酸代谢的适应性机制具有重要意义。