Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation.
Hepatocytes in collagen sandwich: evidence for transcriptional and translational regulation.
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DOI：
10.1083/jcb.116.4.1043
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发表时间：
1992-02
期刊：
影响因子：
--
通讯作者：
Yarmush ML
中科院分区：
文献类型：
--
作者：
Dunn JC;Tompkins RG;Yarmush ML
研究了细胞外基质形态对培养肝细胞组织特异性功能的影响。将夹在两层胶原凝胶之间的成年大鼠肝细胞与单层胶原凝胶培养的细胞进行比较，以了解总RNA含量、白蛋白特异性mRNA水平、白蛋白基因转录率和白蛋白mRNA翻译率的差异。在三明治系统中，成年肝细胞的白蛋白mRNA水平与正常肝脏的白蛋白mRNA水平保持了至少六周，而在单凝胶系统中，白蛋白mRNA水平迅速下降。培养1周后，单凝胶体系中的肝细胞在覆盖第二层胶原凝胶时，可诱导其恢复高水平的白蛋白mRNA和白蛋白产量。此外，与单凝胶系统中的细胞相比，夹在中间的肝细胞保持了显著更高的转录活性。除了转录控制外，最终的白蛋白生成速率还取决于翻译速率，翻译速率随着培养时间的增加而增加，并在一到两周内达到平稳期。随着培养时间的推移，在三明治和单凝胶系统中都观察到这种翻译活性的增加，因此，似乎与细胞外基质的配置无关。
The influence of extracellular matrix configuration on the tissue- specific function of cultured hepatocytes was investigated. Adult rat hepatocytes sandwiched between two layers of collagen gel were compared to cells cultured on a single layer of collagen gel for differences in the total RNA content, the level of albumin-specific mRNA, the rate of albumin gene transcription, and the rate of albumin mRNA translation. Adult hepatocytes in the sandwich system maintained the level of albumin mRNA similar to that found in the normal liver for at least six weeks, whereas the level of albumin mRNA declined rapidly in the single gel system. After one week of culture, hepatocytes in the single gel system could be induced to recover the high level of albumin mRNA and albumin production when a second layer of collagen gel was overlaid at that time. Furthermore, sandwiched hepatocytes maintained significantly higher transcriptional activity compared to cells in the single gel system. In addition to transcriptional control, the ultimate rate of albumin production was shown to depend on the rate of translation, which increased with culture time and reached a plateau in one to two weeks. This increase in translational activity over time in culture was observed in both the sandwich and the single gel systems and, thus, appeared to be independent of the configuration of extracellular matrix.