Sweet taste receptor subunit T1R3 regulates casein secretion and phosphorylation of STAT5 in mammary epithelial cells
Sweet taste receptor subunit T1R3 regulates casein secretion and phosphorylation of STAT5 in mammary epithelial cells
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DOI：
10.1016/j.bbamcr.2023.119448
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发表时间：
2023-03-06
影响因子：
5.1
通讯作者：
Nishimura, Takanori
中科院分区：
文献类型：
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作者：
Kobayashi, Ken;Han, Liang;Nishimura, Takanori
在哺乳期间，顶膜上的乳腺上皮细胞（MEC）与牛奶中的乳糖接触，而基底外侧膜上的MEC与血液中的葡萄糖接触。葡萄糖和乳糖都是甜味受体感知的甜味剂。此前，我们已经证明，基底外侧膜而非顶膜上的乳糖暴露会抑制 MEC 中酪蛋白的产生和 STAT5 的磷酸化。然而，目前尚不清楚 MEC 是否具有甜味受体。在本研究中，我们证实甜味受体亚基T1R3同时存在于MEC的顶膜和基底外侧膜中。随后，我们使用细胞培养模型研究了顶端和基底外侧三氯蔗糖作为甜味受体配体的影响。在此模型中，上层和下层介质被 MEC 层分隔开，并具有渗透性较小的紧密连接。结果显示，在缺乏葡萄糖的情况下，顶端和基底外侧三氯蔗糖均诱导 STAT5 磷酸化，STAT5 是产奶的正转录因子。相比之下，T1R3抑制剂基底外侧lactisole在葡萄糖存在的情况下减少磷酸化STAT5并分泌酪蛋白。此外，在存在葡萄糖的情况下将顶膜暴露于三氯蔗糖会抑制STAT5的磷酸化。同时，MEC 中 GLUT1 部分从基底外侧膜转移至细胞质。这些结果表明 T1R3 作为甜味受体发挥作用，并密切参与 MEC 中酪蛋白的产生。
During lactation, mammary epithelial cells (MECs) on the apical membrane are in contact with lactose in milk, while MECs on the basolateral membrane are in contact with glucose in blood. Both glucose and lactose are sweeteners that are sensed by a sweet taste receptor. Previously, we have shown that lactose exposure on the basolateral membrane, but not the apical membrane, inhibits casein production and phosphorylation of STAT5 in MECs. However, it remains unclear whether MECs have a sweet taste receptor. In this study, we confirmed that the sweet taste receptor subunit T1R3 existed in both the apical and basolateral membranes of MECs. Subse-quently, we investigated the influence of apical and basolateral sucralose as a ligand for the sweet taste receptor using a cell culture model. In this model, upper and lower media were separated by the MEC layer with less-permeable tight junctions. The results showed in the absence of glucose, both apical and basolateral sucralose induced phosphorylation of STAT5, which is a positive transcriptional factor for milk production. In contrast, the T1R3 inhibitor basolateral lactisole reducing phosphorylated STAT5 and secreted caseins in the presence of glucose. Furthermore, exposure of the apical membrane to sucralose in the presence of glucose inhibited the phosphorylation of STAT5. Simultaneously, GLUT1 was partially translocated from the basolateral membrane to the cytoplasm in MECs. These results suggest that T1R3 functions as a sweet receptor and is closely involved in casein production in MECs.