Abstract
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.
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Funding
This work was funded by the Education Department of Liaoning Province (No. LF2020005, JYTMS20231058), Liaoning Province Natural Science and Technology Plan Guidance Project (No. 2019-ZD-0301), and Doctoral Scientific Research Foundation of Liaoning Normal University (BS2020L002).
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Yan Chi contributed to the study conception and design. Yingying Zhu prepared Figs. 1, 2, 3, 4, and 5. Qipeng Zhang prepared Figs. 6, 7. Primary cell isolation was performed by Jilong Pan and Jindi Liu. Molecular docking was performed by Lei Qian. Material preparation were performed by Tiesong Li and Hao Wang. Ting Zhu helped us analyze the phylogenetic trees. Yue Pang and Qingwei Li provided the lab conditions. The manuscript was written by Yan Chi and Qipeng Zhang. Yan Chi will revise the manuscript. All of the authors reviewed the manuscript and approved the final manuscript.
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The animal experiments were performed in accordance with the regulations of the Animal Welfare and Research Ethics Committee of the Institute of Dalian Medical University’s Animal Care protocol (Permit Number: SCXK2008-0002).
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10695_2024_1324_MOESM4_ESM.tif
Supplementary file4 Supplementary Figure 1. Multiple sequence alignments of SLC10a1 in the indicated species. The red arrows represent conserved amino acid sites that are involved in bile acid transport between L-NTCP and other higher vertebrate orthologs. (TIF 16137 KB)
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Zhu, Y., Zhang, Q., Pan, J. et al. Evolutionary analysis of SLC10 family members and insights into function and expression regulation of lamprey NTCP. Fish Physiol Biochem (2024). https://doi.org/10.1007/s10695-024-01324-7
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DOI: https://doi.org/10.1007/s10695-024-01324-7