Variant (MDCK) kidney epithelial cells altered in response to inducers of dome formation and differentiation.
Variant (MDCK) kidney epithelial cells altered in response to inducers of dome formation and differentiation.
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变异（MDCK）肾上皮细胞响应圆顶形成和分化的诱导剂而发生改变。
DOI：
10.1002/jcp.1041220108
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发表时间：
1985
影响因子：
5.6
通讯作者：
Lever,JE
中科院分区：
文献类型：
--
作者：
Lever,JE
MDCK肾上皮细胞系的融合培养物显示圆顶形成，这是细胞-细胞和细胞-基质相互作用影响的经上皮液体转运的结果。圆顶的形成可由双乙酰胺（HMBA）或二甲基甲酰胺（DMF）诱导，这些化合物被称为细胞分化诱导剂（Lever，1979 b）。对非选择性来源于MDCK细胞系的集落中圆顶形成表型发生率的分析表明，诱导剂招募了更多的细胞群以表达圆顶形成。分离出变异MDCK细胞系，其在对诱导剂的反应中不同于亲本细胞系，同时保留立方上皮形态。在5个独立分离和克隆的MDCK变体中，DMF不能诱导圆顶形成，HMBA仅略微增加圆顶形成。这种表型也与细胞对塑料基质的粘附性增加有关。共培养实验的结果表明，变异细胞的DMF无反应表型可通过细胞间接触野生型细胞而部分克服。通过哇巴因敏感性Rb+摄取评估的钠泵转运活性在“野生型”诱导剂应答克隆中被HMBA和DMF部分抑制。相比之下，DMF不抑制DMF无反应的变体克隆中的哇巴因敏感性Rb+摄取，并且HMBA的钠泵抑制作用大大减弱。变异克隆中诱导剂改变的钠泵调节与其改变的圆顶形成反应之间的密切对应关系加强了我们先前的结论（Kennedy和Lever，1984），即钠泵调节与诱导剂作用机制密切相关。总之，这些发现表明细胞-细胞相互作用、细胞-基质相互作用和钠泵调节调节了该细胞系的分化表型。
Confluent cultures of the MDCK kidney epithelial cell line exhibit dome formation, a result of transepithelial fluid transport influenced by cell‐cell and cell‐substratum interaction. Dome formation was inducible by hexamethylene bisacetamide (HMBA) or dimmethylformamide (DMF), compounds known as inducers of cell differentiation (Lever, 1979b). Analysis of the incidence of the dome‐forming phenotype in colonies derived nonselectively from the MDCK cell line suggested that inducers recruit an increased fraction of the cell population to express dome formation. Variant MDCK cell lines were isolated which differed from the parental line in response to inducers while retaining cuboidal epithelial morphology. In five independently isolated and cloned MDCK variants, dome formation was not inducible by DMF and only marginally increased by HMBA. This phenotype was also associated with increased cell adhesiveness to a plastic substratum. Results from cocultivation experiments suggested that the DMF‐unresponsive phenotype of variant cells may be partially overcome by cell‐cell contact with wild‐type cells. Sodium pump transport activity assessed by ouabain‐sensitive Rb+uptake was partially inhibited by HMBA and by DMF in a “wild‐type” inducer‐responsive clone. By contrast, DMF did not inhibit ouabain‐sensitive Rb+uptake in DMF‐unresponsive variant clones, and sodium pump inhibition by HMBA was greatly diminished. This close correspondence between altered sodium pump modulation by inducers in variant clones and their altered dome‐forming response reinforces our previous conclusions (Kennedy and Lever, 1984) that sodium pump modulation is closely associated with mechanisms of inducer action. Taken together, these findings implicate cell‐cell interaction, cell‐substratum interaction and sodium pump modulation in regulation of the differentiated phenotype of this cell line.