Laboratory of Dairy Food Science, Research Faculty of Agriculture, Hokkaido University, Sapporo, Japan.
Histochem Cell Biol. 2011 Nov;136(5):587-94. doi: 10.1007/s00418-011-0863-6. Epub 2011 Sep 13.
Tight junctions (TJs) are the most apical junctional complexes and restrict the fluid flux through the paracellular pathway. In the mammary glands, the tightness of TJs occurs shortly after parturition to prevent the leakage of milk components from the lumen and the loosening of TJs is induced immediately after weaning. Claudins are transmembrane proteins, and their composition at the apical-most regions determines the permeability of TJs. In this study, we investigated the localization and expression patterns of claudin-3 and -4 in the mammary glands around the lactation period because it is unclear how claudins construct mammary TJs in the apical-most regions. Our results showed that claudin-3 and -4 change not only their level of expression but also their localization in the processes of parturition, lactation, and weaning. Claudin-3 was concentrated in the apical-most regions during lactation, whereas claudin-4 gradually decreased at the beginning of lactation and increased drastically immediately after weaning. The qualitative change of claudin-3 was also identified by western blotting analysis as an additional band around the lactation period. In addition, parts of the mammary epithelial cells showed intensive positive reactions to claudin-4 in the lateral membrane and cytoplasm after weaning, concurrently with the involution mammary glands. These results indicate that claudin-3 in the apical-most regions maintains the impermeable TJs during lactation, and claudin-4 contributes to the permeability changes of TJs immediately after parturition and weaning.
紧密连接（TJs）是最顶端的连接复合体，限制了细胞旁途径的流体通量。在乳腺中，TJs 的紧密性在分娩后不久发生，以防止乳成分从腔中泄漏，而 TJs 的松弛在断奶后立即发生。 Claudin 是跨膜蛋白，其在最顶端区域的组成决定了 TJs 的通透性。在这项研究中，我们研究了 Claudin-3 和 -4 在哺乳期周围乳腺中的定位和表达模式，因为不清楚 Claudin 如何在最顶端区域构建乳腺 TJs。我们的结果表明，Claudin-3 和 -4 的表达水平和定位不仅在分娩、泌乳和断奶过程中发生变化。Claudin-3 在泌乳期集中在最顶端区域，而 Claudin-4 在泌乳开始时逐渐减少，断奶后急剧增加。Western blot 分析还鉴定了 Claudin-3 的定性变化，即在泌乳期周围出现了额外的条带。此外，部分乳腺上皮细胞在断奶后在侧膜和细胞质中对 Claudin-4 表现出强烈的阳性反应，同时乳腺也在退化。这些结果表明，Claudin-3 在最顶端区域在泌乳期间维持了不可渗透的 TJs，而 Claudin-4 有助于分娩和断奶后 TJs 的通透性变化。
