Retinoids as important regulators of terminal differentiation: examining keratin expression in individual epidermal cells at various stages of keratinization.
Retinoids as important regulators of terminal differentiation: examining keratin expression in individual epidermal cells at various stages of keratinization.
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DOI：
10.1083/jcb.105.1.427
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发表时间：
1987-07
期刊：
影响因子：
--
通讯作者：
Fuchs E
中科院分区：
文献类型：
--
作者：
Kopan R;Traska G;Fuchs E
当人类表皮细胞被播种在胶原蛋白和成纤维细胞的漂浮筏上时，它们在气液界面分层。基底上细胞合成大的II型（K1）和I型（K10/K11）角蛋白，具有皮肤终末分化的特征。在早期的培养中，大的II型角蛋白的表达似乎先于它们的I型伙伴的表达。后来，所有的基底上细胞都表达这两种类型，这表明K1角蛋白的积累达到临界水平可能是K10和K11表达的必要刺激。在培养基中加入维甲酸或将培养液浸泡在正常培养基中，可完全抑制终末分化特异性角蛋白的表达。在深层培养中，通过血清脱脂油去除维生素A恢复角化过程。相比之下，钙和转化生长因子- β不影响在类维生素a存在下生长的角化细胞中大角蛋白的表达，尽管已知它们可以诱导终分化的某些形态特征。raft培养基中的维甲酸不仅抑制了大角蛋白的表达，而且还诱导了两种在体内通常不在表皮中表达的新角蛋白的合成。免疫荧光将其中一种角蛋白K19定位到分层培养的几个分离细胞上。相反，另一种角蛋白K13均匀地出现在培养物的几个外层。有趣的是，在培养过程中，K13的表达与类维甲酸介导的细胞间相互作用中断的梯度密切相关。这些数据表明，K13诱导可能在某种程度上与层状鳞状上皮组织中基底上细胞间桥粒接触数量或强度的减少有关。
When human epidermal cells were seeded on floating rafts of collagen and fibroblasts, they stratified at the air-liquid interface. The suprabasal cells synthesized the large type II (K1) and type I (K10/K11) keratins characteristic of terminal differentiation in skin. At earlier times in culture, expression of the large type II keratins appeared to precede the expression of their type I partners. At later times, all suprabasal cells expressed both types, suggesting that the accumulation of a critical level of K1 keratin may be a necessary stimulus for K10 and K11 expression. Expression of the terminal differentiation-specific keratins was completely suppressed by adding retinoic acid to the culture medium, or by submerging the cultures in normal medium. In submerged cultures, removal of vitamin A by delipidization of the serum restored the keratinization process. In contrast, calcium and transforming growth factor-beta did not influence the expression of the large keratins in keratinocytes grown in the presence of retinoids, even though they are known to induce certain morphological features of terminal differentiation. Retinoic acid in the raft medium not only suppressed the expression of the large keratins, but, in addition, induced the synthesis of two new keratins not normally expressed in epidermis in vivo. Immunofluorescence localized one of these keratins, K19, to a few isolated cells of the stratifying culture. In contrast, the other keratin, K13, appeared uniformly in a few outer layers of the culture. Interestingly, K13 expression correlated well with the gradient of retinoid-mediated disruptions of intercellular interactions in the culture. These data suggest that K13 induction may in some way relate to the reduction in either the number or the strength of desmosomal contacts between suprabasal cells of stratified squamous epithelial tissues.