Division of Clinical Pharmaceutics, Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281 Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan.
Mol Biol Rep. 2022 Sep;49(9):8685-8692. doi: 10.1007/s11033-022-07709-2. Epub 2022 Jun 29.
The unstirred water layer (UWL) is an integral part of the apical surface of mucosal epithelia and comprises mucins (MUC), for which there are many molecular species. Galectins, a family of β-galactoside-binding lectins, form a lattice barrier on surface epithelial cells by interacting with MUC. Lactose inhibits the galectin-MUC interaction. Therefore, the present study investigated the galectin-MUC interaction in the mucosa of the gastrointestinal tract and its role in intestinal barrier functions.
The effects of lactose hydrate (LH) on the membrane permeability of the rat small intestine and Caco-2 cells were examined. LH enhanced the membrane permeability of the rat small intestine, which contains the UWL, via a transcellular route, for which the UWL is the rate limiting factor. The membrane permeability of Caco-2 cells, in which the UWL is insufficient, was not affected by LH. The apparent permeability coefficient (P) of a paracellular marker was not significantly altered in the rat small intestine or Caco-2 cells treated with LH at any concentration. Furthermore, the P of β-naphthol which is a transcellular marker was not significantly altered in Caco-2 cells treated with LH, but was significantly increased in the rat small intestine in a LH concentration-dependent manner.
The present results demonstrate that the physical barrier has an important function in gastrointestinal membrane permeability, and LH-induced changes increase the transcellular permeability of β-naphthol in rat small intestine.
非搅动水层(UWL)是黏膜上皮的顶表面的一个组成部分,包含许多分子种类的粘蛋白(MUC)。半乳糖凝集素是一种β-半乳糖苷结合凝集素家族,通过与 MUC 相互作用在表面上皮细胞上形成晶格屏障。乳糖抑制半乳糖凝集素-MUC 相互作用。因此,本研究调查了胃肠道黏膜中的半乳糖凝集素-MUC 相互作用及其在肠道屏障功能中的作用。
研究了乳糖水合物(LH)对大鼠小肠和 Caco-2 细胞的膜通透性的影响。LH 通过细胞旁路增强了含有 UWL 的大鼠小肠的膜通透性,UWL 是该途径的限速因素。Caco-2 细胞中 UWL 不足,其膜通透性不受 LH 影响。用 LH 处理任何浓度的大鼠小肠或 Caco-2 细胞,对细胞旁标记物的表观渗透系数(P)没有显著改变。此外,在 Caco-2 细胞中用 LH 处理时,β-萘酚(一种细胞旁路标记物)的 P 没有显著改变,但在大鼠小肠中以 LH 浓度依赖性方式显著增加。
本研究结果表明,物理屏障在胃肠道膜通透性中具有重要作用,LH 诱导的变化增加了大鼠小肠中β-萘酚的细胞旁路通透性。