Stelwagen K, Callaghan M R
Dairy Biotechnology, Ruakura Research Centre, AgResearch, Private Bag 3123, Hamilton, New Zealand.
J Endocrinol. 2003 Aug;178(2):257-64. doi: 10.1677/joe.0.1780257.
Tight junctions (TJs) play an essential role in cell-cell contact between mammary epithelial cells and, as such, play a critical role in cell function. Moreover, calcium (Ca) plays a crucial role in the formation and maintenance of mammary TJs. Given that parathyroid hormone-related peptide (PTHrP) is involved in cellular Ca homeostasis, we postulated a role for PTHrP in the regulation of mammary TJs. The effect of PTHrP(1-34) on TJs was studied in the mouse mammary cell line COMMA-1D by measuring transepithelial electrical resistance across cell monolayers and measuring the expression of TJ proteins. PTHrP stimulated TJ formation but only under conditions where extracellular Ca was limiting. This effect of PTHrP appeared to be indirect and mediated via increased intracellular availability of Ca as a result of increased Ca-channel activity in the apical membrane. The changes in TJs were associated with altered expression of the TJ protein occludin, but expression of the TJ protein claudin-1 was not affected. The effects of PTHrP on mammary TJs are independent of prolactin. In conclusion, PTHrP enhances mammary TJ formation when extracellular Ca is limiting by maintaining intracellular Ca supplies.
紧密连接（TJs）在乳腺上皮细胞之间的细胞间接触中起着至关重要的作用，因此在细胞功能中发挥着关键作用。此外，钙（Ca）在乳腺紧密连接的形成和维持中起着至关重要的作用。鉴于甲状旁腺激素相关肽（PTHrP）参与细胞钙稳态，我们推测PTHrP在乳腺紧密连接的调节中发挥作用。通过测量跨细胞单层的跨上皮电阻并检测紧密连接蛋白的表达，研究了PTHrP(1-34)对小鼠乳腺细胞系COMMA-1D中紧密连接的影响。PTHrP刺激紧密连接的形成，但仅在细胞外钙有限的条件下。PTHrP的这种作用似乎是间接的，是通过增加顶端膜上钙通道活性导致细胞内钙可用性增加来介导的。紧密连接的变化与紧密连接蛋白闭合蛋白的表达改变有关，但紧密连接蛋白Claudin-1的表达不受影响。PTHrP对乳腺紧密连接的作用独立于催乳素。总之，当细胞外钙有限时，PTHrP通过维持细胞内钙供应来增强乳腺紧密连接的形成。
