Sun Tung-Tien
Epithelial Biology Unit, Department of Dermatology, New York University Cancer Institute, Medical School, 550 First Ave., New York, NY 10016, USA.
Am J Physiol Renal Physiol. 2006 Jul;291(1):F9-21. doi: 10.1152/ajprenal.00035.2006. Epub 2006 Apr 11.
The differentiation of cultured stratified epithelial cells can deviate significantly from that of normal epithelium, leading to suggestions that cultured cells undergo abnormal differentiation, or a truncated differentiation. Thus cultured epidermal and corneal epithelial cells stop synthesizing their tissue-specific keratin pair K1/K10 and K3/K12, respectively. The replacement of these keratins in the suprabasal compartment by K6/K16 keratins that are made by all stratified squamous epithelia during hyperplasia rules out a truncated differentiation. Importantly, the keratin pattern of in vivo corneal epithelium undergoing wound repair mimics that of cultured rabbit corneal epithelial cells. Although cultured urothelial cells continue to synthesize uroplakins, which normally form two-dimensional crystalline urothelial plaques covering almost the entire apical urothelial surface, these proteins do not assemble into crystals in cultured cells. Cultured epithelial cells can, however, rapidly regain normal differentiation on the removal of mitogenic stimuli, the use of a suitable extracellular matrix, or the transplantation of the cells to an in vivo, nonmitogenic environment. These data suggest that cultured epithelial cells adopt altered differentiation patterns mimicking in vivo regenerating or hyperplastic epithelia. Blocking the synthesis of tissue-specific differentiation products, such as the K1 and K10 keratins designed to form extensive disulfide cross-links in cornified cells, or the assembly of uroplakin plaques allows epithelial cells to better migrate and proliferate, activities that are of overriding importance during wound repair. Cultured urothelial and other stratified epithelial cells provide excellent models for studying the regulation of the synthesis and assembly of differentiation products, a key cellular process during epithelial wound repair.
培养的分层上皮细胞的分化可能与正常上皮细胞的分化有显著偏差，这导致有人认为培养的细胞经历了异常分化或截断分化。因此，培养的表皮和角膜上皮细胞分别停止合成其组织特异性角蛋白对K1/K10和K3/K12。在增生过程中，所有分层鳞状上皮细胞产生的K6/K16角蛋白取代了基底层以上区域的这些角蛋白，这排除了截断分化的可能性。重要的是，正在进行伤口修复的体内角膜上皮细胞的角蛋白模式与培养的兔角膜上皮细胞的角蛋白模式相似。尽管培养的尿路上皮细胞继续合成尿路上皮素，这些尿路上皮素通常形成覆盖几乎整个尿路上皮顶端表面的二维晶体尿路上皮斑块，但这些蛋白质在培养细胞中不会组装成晶体。然而，在去除促有丝分裂刺激、使用合适的细胞外基质或将细胞移植到体内非促有丝分裂环境后，培养的上皮细胞可以迅速恢复正常分化。这些数据表明，培养的上皮细胞采用了改变的分化模式，模仿体内再生或增生的上皮细胞。阻断组织特异性分化产物的合成，如旨在在角质化细胞中形成广泛二硫键交联的K1和K10角蛋白，或尿路上皮斑块的组装，可使上皮细胞更好地迁移和增殖，这些活动在伤口修复过程中至关重要。培养的尿路上皮细胞和其他分层上皮细胞为研究分化产物合成和组装的调控提供了极好的模型，这是上皮伤口修复过程中的一个关键细胞过程。
