Yuki Kurobe-Takashima

Ph.D. student

The University of Tokyo

Yuki Kurobe-Takashima is a second-year Ph.D. student and JSPS fellow at the Graduate School of Agricultural and Life Sciences, the University of Tokyo, Japan. She received a bachelor’s degree in nutrition and food science from Ochanomizu University and a master’s in agriculture from the University of Tokyo. Her current research focuses on the mechanisms of intestinal bile acid transport systems and polyphenols that are beneficial to human health. Her ultimate research goal is to understand comprehensively how food-beneficial compounds are absorbed into the body and express their functions, which she believes is essential in providing evidence on functional food. She is also interested in post-translational modification and trafficking of membrane transporters and the mechanisms that maintain their homeostasis. In her “off” time, Yuki likes to cook, travel, and eat with her family.

Members of the organic anion transporting polypeptide family contribute to bile acid uptake in the human intestinal epithelium Caco-2 cell model

Intestinal bile acid transport system is attracting attention as a therapeutic target for metabolic syndromes and inflammation-related diseases. Bile acid transport in the human intestine is mediated by the apical sodium-dependent bile acid transporter (ASBT). Organic anion transporting polypeptides (OATPs) also mediate bile acid transport in other organs and is expressed ubiquitously, while their role in the intestinal bile acid uptake is not clear. Caco-2 cells, a cell line derived from human colonic adenoma, are frequently used as an intestinal epithelium model in bile acid related studies; however, the bile acid transport mechanism in this cell has yet to be elucidated. To address bile acid uptake mechanism in Caco-2 cells with OATPs’s involvement, we conducted bile acid (i.e., taurocholic acid; TC) uptake assays followed by kinetic analysis in Caco-2 cells, OATPs- and ASBT-overexpressing cells. Eadie-Hofstee plot of TC uptake in the Caco-2 cells showed biphasic kinetics, suggesting there was more than one transporter mediating bile acid in the cells. To identify a transporter other than ASBT in Caco-2 cells, we screened OATPs for their TC uptake in OATP-overexpressing HEK293T cells. OATP1A2 and OATP1B3 mediated TC uptake, and together with kinetic analysis and gene expression analysis, both were suggested to mediate TC uptake in Caco-2 2 cells. Our data illustrated a specific feature of TC uptake in Caco-2 cells that may offer a therapeutic target for intestinal inflammation and cancer studies.