Mouse proximal tubular cell-cell adhesion inhibits apoptosis by a cadherin-dependent mechanism
Mouse proximal tubular cell-cell adhesion inhibits apoptosis by a cadherin-dependent mechanism
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DOI：
10.1152/ajprenal.2000.278.5.f758
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发表时间：
2000-05-01
影响因子：
4.2
通讯作者：
Lieberthal, W
中科院分区：
文献类型：
--
作者：
Bergin, E;Levine, JS;Lieberthal, W
已知上皮细胞与基质的粘附可抑制细胞凋亡。然而，细胞-细胞粘附在介导细胞存活中的作用仍不确定。小鼠近端小管（MPT）细胞的原代培养用于研究细胞-细胞粘附在促进存活中的作用。当MPT细胞同时被剥夺细胞-基质和细胞-细胞粘附时，MPT细胞凋亡。然而，当培养在琼脂糖包被的培养皿中（防止细胞-基质粘附）和高细胞密度（允许细胞-细胞相互作用）时，MPT细胞彼此粘附并保持活力。E-cadherin在悬浮、聚集细胞中的表达随时间增加而增加。一种含有His-Ala-Val （HAV）的肽抑制血友病E-cadherin结合，阻止细胞-细胞聚集，促进悬浮MPT细胞凋亡。相比之下，抑制悬浮细胞之间由pl整合素介导的潜在相互作用并不会阻止悬浮细胞的聚集或存活。悬浮中的细胞聚集激活了磷脂酰肌醇3-激酶（PI3K），这一事件因HAV肽的存在而显着减少。PI3K抑制剂LY-294002也能抑制悬浮细胞的存活。总之，我们提供的新证据表明，当剥夺正常的细胞-基质相互作用时，MPT细胞可以以钙粘蛋白依赖的方式相互粘附并保持活力。聚集细胞的存活依赖于PI3K的活化。
Adhesion of epithelial cells to matrix is known to inhibit apoptosis. However, the role of cell-cell adhesion in mediating cell survival remains uncertain. Primary cultures of mouse proximal tubular (MPT) cells were used to examine the role of cell-cell adhesion in promoting survival. When MPT cells were deprived of both cell-matrix and cell-cell adhesion, they died by apoptosis. However, when incubated in agarose-coated culture dishes (to prevent cell-matrix adhesion) and at high cell density (to allow cell-cell interactions), MPT cells adhered to one another and remained viable. Expression of E-cadherin among suspended, aggregating cells increased with time. A His-Ala-Val (HAV)-containing peptide that inhibits hemophilic E-cadherin binding prevented cell-cell aggregation and promoted apoptosis of MPT cells in suspension. By contrast, inhibition of potential pl-integrin-mediated interactions between cells in suspension did not prevent either aggregation or survival of suspended cells. Aggregation of cells in suspension activated phosphatidylinositol 3-kinase (PI3K), an event that was markedly reduced by the presence of the HAV peptide. LY-294002, an inhibitor of PI3K, also inhibited survival of suspended cells. In summary, we provide novel evidence that MPT cells, when deprived of normal cell-matrix interactions, can adhere to one another in a cadherin-dependent fashion and remain viable. Survival of aggregated cells depends on activation of PI3K.