Forced expression of keratin 16 alters the adhesion, differentiation, and migration of mouse skin keratinocytes
Forced expression of keratin 16 alters the adhesion, differentiation, and migration of mouse skin keratinocytes
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DOI：
10.1091/mbc.11.10.3315
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发表时间：
2000-10-01
影响因子：
3.3
通讯作者：
Coulombe, PA
中科院分区：
文献类型：
--
作者：
Wawersik, M;Coulombe, PA
皮肤损伤导致角蛋白K6、K16和K17的诱导，伴随着角化细胞的活化用于上皮再形成。人K16在转基因小鼠皮肤上皮中的强制表达会导致一种模拟角质形成细胞活化的几个方面的表型。在原代培养物中分析了两种类型的转基因角质形成细胞，其具有人K16或K16-C14嵌合cDNA的强制表达，以评估K16表达在细胞水平上的影响。高表达K16-C14和低表达K16的转基因角质形成细胞在所有测试方面与野生型相似。相反，高表达K16的转基因角质形成细胞显示出平板接种效率和钙诱导分化的改变，但增殖正常。与对照相比，K16转基因皮肤外植体中角质形成细胞的迁移减少。最后，一个子集的高K16表达的转基因角质形成细胞发展的主要变化，在组织角蛋白丝的时间和钙浓度依赖性的方式。这些变化与角蛋白含量的改变相一致，而K16蛋白的稳态水平保持稳定。我们的结论是，强迫表达的K16祖皮肤角质形成细胞直接影响的属性，如粘附，分化和迁移，这些影响取决于其羧基末端内所含的决定因素。
Injury to the skin results in an induction of keratins K6, K16, and K17 concomitant with activation of keratinocytes for reepithelialization. Forced expression of human K16 in skin epithelia of transgenic mice causes a phenotype that mimics several aspects of keratinocyte activation. Two types of transgenic keratinocytes, with forced expression of either human K16 or a K16-C14 chimeric cDNA, were analyzed in primary culture to assess the impact of K16 expression at a cellular level. High K16-C14-expressing and low K16-expressing transgenic keratinocytes behave similar to wild ty-pe in all aspects tested. Ln contrast, high K16-expressing transgenic keratinocytes show alterations in plating efficiency and calcium-induced differentiation, but proliferate normally. Migration of keratinocytes is reduced in K16 transgenic skin explants compared with controls. Finally, a subset of high K16-expressing transgenic keratinocytes develops major changes in the organization of keratin filaments in a time- and calcium concentration-dependent manner. These changes coincide with alterations in keratin content while the steady-state levels of K16 protein remain stable. We conclude that forced expression of K16 in progenitor skin keratinocytes directly impacts properties such as adhesion, differentiation, and migration, and that these effects depend upon determinants contained within its carboxy terminus.