Castro-Muñozledo Federico, Velez-DelValle Cristina, Marsch-Moreno Meytha, Hernández-Quintero Miriam, Kuri-Harcuch Walid
Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN Apdo, Postal 14-740, 07000, Mexico City, Mexico,
Histochem Cell Biol. 2015 Jan;143(1):45-57. doi: 10.1007/s00418-014-1262-6. Epub 2014 Aug 21.
The role of vimentin (Vim) in diploid epithelial cells is not well known. To understand its biological function, we cultured human epidermal keratinocytes under conditions that support migration, proliferation, stratification and terminal differentiation. We identified a keratinocyte subpopulation that shows a p63(+)/α5β1(bright) phenotype and displays Vim intermediate filaments (IFs) besides their keratin IF network. These cells were mainly located at the proliferative/migratory rim of the growing colonies; but also, they were scarce and scattered or formed small groups of basal cells in confluent stratified epithelia. Stimulation of cells with EGF and wounding experiments in confluent arrested epithelia increased the number of Vim(+) keratinocytes in an extent higher to the expected for a cell population doubling. BrdU labeling demonstrated that most of the proliferative cells located at the migratory border of the colony have Vim, in contrast with proliferative cells located at the basal layer at the center of big colonies which lacked of Vim IFs, suggesting that Vim expression was not solely linked to proliferation. Therefore, we silenced Vim mRNA in the cultured keratinocytes and observed an inhibition of colony growth. Such results, together with long-term cultivation assays which showed that Vim might be associated to pattern formation in cultured epithelia, suggest that Vim expression is essential for a highly motile phenotype, which is necessary for keratinocyte colony growth and possibly for development and wound healing. Vim(+)/p63(+)/α5β1(bright) epithelial cells may play a significant physiological role in embryonic morphogenetic movements; wound healing and other pathologies such as carcinomas and hyperproliferative diseases.
波形蛋白(Vim)在二倍体上皮细胞中的作用尚不明确。为了解其生物学功能,我们在支持迁移、增殖、分层和终末分化的条件下培养人表皮角质形成细胞。我们鉴定出一个角质形成细胞亚群,其表现出p63(+) /α5β1(明亮)表型,除了角蛋白中间丝网络外还显示波形蛋白中间丝(IFs)。这些细胞主要位于生长菌落的增殖/迁移边缘;此外,它们稀少且分散,或在汇合的分层上皮中形成小群基底细胞。用表皮生长因子(EGF)刺激细胞以及在汇合停滞的上皮中进行创伤实验,使波形蛋白阳性角质形成细胞的数量增加,其增加程度高于细胞群体加倍预期的程度。5-溴脱氧尿嘧啶核苷(BrdU)标记表明,位于菌落迁移边界的大多数增殖细胞具有波形蛋白,这与位于大菌落中心基底层的缺乏波形蛋白IFs的增殖细胞形成对比,提示波形蛋白表达并非仅与增殖相关。因此,我们在培养的角质形成细胞中使波形蛋白mRNA沉默,并观察到菌落生长受到抑制。这些结果,连同长期培养实验表明波形蛋白可能与培养上皮中的模式形成有关,提示波形蛋白表达对于高度运动性表型至关重要,而这种表型对于角质形成细胞菌落生长以及可能对于发育和伤口愈合是必需的。波形蛋白(+) / p63(+) /α5β1(明亮)上皮细胞可能在胚胎形态发生运动、伤口愈合以及其他病理情况如癌和增殖性疾病中发挥重要的生理作用。