Adams J C, Watt F M
Keratinocyte Laboratory, Imperial Cancer Research Fund, London, UK.
Nature. 1989 Jul 27;340(6231):307-9. doi: 10.1038/340307a0.
In the epidermis proliferation of keratinocytes is restricted to the basal layer, which is in contact with the basement membrane, and cells undergo terminal differentiation as they move upwards through the suprabasal layers. In stratified cultures of human keratinocytes, upward migration is a consequence, not a cause, of terminal differentiation and occurs because keratinocytes become less adhesive to their substratum and to one another. Most keratinocytes can be induced to differentiate to completion by placing them in suspension in methylcellulose: within 12 h DNA synthesis is irreversibly inhibited and by 24 h most cells express involucrin (ref 4; P. A. Hall, J.C.A. and F.M.W., unpublished observations). Here we report that when fibronectin is added to the methylcellulose, keratinocytes still withdraw from the cell cycle, but induction of involucrin expression is largely inhibited. The effect of fibronectin is concentration- and time-dependent and is mediated by a receptor of the integrin family. These results provide an explanation for why overt terminal differentiation is normally restricted to suprabasal cells, whereas cell-cycle withdrawal occurs within the basal layer; they also have important implications for the mechanism of epidermal wound healing. Furthermore, our data show that the binding of an extracellular matrix protein to its receptor can regulate differentiated gene expression in the absence of changes in cell shape.
在表皮中，角质形成细胞的增殖仅限于与基底膜接触的基底层，当细胞向上穿过基底上层时会经历终末分化。在人角质形成细胞的分层培养中，向上迁移是终末分化的结果而非原因，其发生是因为角质形成细胞对其基质和彼此的粘附性降低。通过将大多数角质形成细胞悬浮于甲基纤维素中，可诱导它们完成分化：12小时内DNA合成被不可逆抑制，24小时时大多数细胞表达兜甲蛋白（参考文献4；P.A. Hall、J.C.A.和F.M.W.，未发表的观察结果）。我们在此报告，当向甲基纤维素中添加纤连蛋白时，角质形成细胞仍会退出细胞周期，但兜甲蛋白表达的诱导受到很大抑制。纤连蛋白的作用具有浓度和时间依赖性，且由整合素家族的受体介导。这些结果解释了为何明显的终末分化通常仅限于基底上层细胞，而细胞周期退出发生在基底层；它们对表皮伤口愈合机制也具有重要意义。此外，我们的数据表明，在细胞形状未改变的情况下，细胞外基质蛋白与其受体的结合可调节分化基因的表达。
