The role of FLVCR1 and FLVCR2 in choline transport in the Caco-2 intestinal epithelial cell model and rat small intestine

IF 4.2 2区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2025-05-02 DOI:10.1016/j.bbadis.2025.167883

Tomoya Yasujima , Chitaka Namba , Yosuke Azuma , Yutaro Shinoda , Isamu Matake , Mione Yamasaki , Haruka Morimoto , Mana Namai , Hiroyuki Kusuhara , Katsuhisa Inoue , Takahiro Yamashiro , Hiroaki Yuasa

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引用次数: 0

Abstract

Choline is a vital cationic nutrient for maintaining organismal homeostasis, partially synthesized in the liver but primarily obtained from dietary sources. While previous studies have explored mechanisms of choline absorption in intestinal cells, the precise roles of specific transporters remain to be fully elucidated. This study aimed to investigate the roles of the choline transporters feline leukemia virus subgroup C receptor 1 (FLVCR1) and FLVCR2. Using MDCKII cells expressing human FLVCR1 or FLVCR2, the study revealed that FLVCR1 facilitates choline efflux from the basolateral membrane, while FLVCR2 enables choline uptake through the apical membrane. Functional analyses of FLVCR1 and FLVCR2 variants identified mutations that significantly reduce choline uptake activity. Knockdown experiments in Caco-2 cells resulted in significantly reduced cellular uptake of choline. Functional analysis of choline transport in the everted tissue sacs of the rat small intestine suggested that Flvcr2 aids intestinal choline uptake. Conclusively, the findings of this study indicate that FLVCR1 and FLVCR2 work cumulatively to regulate intestinal choline absorption. These findings provide novel insights into the roles of FLVCR1 and FLVCR2 and offer bases for further research into choline transport mechanisms in the small intestine.

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FLVCR1和FLVCR2在Caco-2肠上皮细胞模型和大鼠小肠胆碱转运中的作用

胆碱是维持机体内稳态的一种重要的阳离子营养素，部分在肝脏中合成，但主要从饮食中获得。虽然以前的研究已经探索了肠细胞吸收胆碱的机制，但特定转运体的确切作用仍有待充分阐明。本研究旨在探讨胆碱转运体猫白血病病毒亚群C受体1 （FLVCR1）和FLVCR2的作用。使用表达人FLVCR1或FLVCR2的MDCKII细胞，研究发现FLVCR1促进胆碱从基底外侧膜流出，而FLVCR2促进胆碱通过顶膜摄取。FLVCR1和FLVCR2变异的功能分析鉴定出显著降低胆碱摄取活性的突变。Caco-2细胞的敲低实验导致细胞对胆碱的摄取显著减少。对大鼠小肠外翻组织囊胆碱转运的功能分析表明，Flvcr2有助于肠胆碱摄取。综上所述，本研究结果表明，FLVCR1和FLVCR2在调节肠道胆碱吸收方面具有累积作用。这些发现为FLVCR1和FLVCR2的作用提供了新的见解，并为进一步研究胆碱在小肠中的转运机制提供了基础。

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来源期刊

Biochimica et biophysica acta. Molecular basis of disease 生物-生化与分子生物学

CiteScore

12.30

自引率

0.00%

发文量

218

审稿时长

32 days

期刊介绍： BBA Molecular Basis of Disease addresses the biochemistry and molecular genetics of disease processes and models of human disease. This journal covers aspects of aging, cancer, metabolic-, neurological-, and immunological-based disease. Manuscripts focused on using animal models to elucidate biochemical and mechanistic insight in each of these conditions, are particularly encouraged. Manuscripts should emphasize the underlying mechanisms of disease pathways and provide novel contributions to the understanding and/or treatment of these disorders. Highly descriptive and method development submissions may be declined without full review. The submission of uninvited reviews to BBA - Molecular Basis of Disease is strongly discouraged, and any such uninvited review should be accompanied by a coverletter outlining the compelling reasons why the review should be considered.