Bernot Kelsie M, Coulombe Pierre A, McGowan Kevin M
Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Invest Dermatol. 2002 Nov;119(5):1137-49. doi: 10.1046/j.1523-1747.2002.19518.x.
The morphogenesis of skin epithelia and adult hair follicle cycling both require integrated signaling between the epithelium and underlying mesenchyme. Because of their unique regulation, keratin intermediate filaments represent useful markers for the analysis of determination and differentiation processes in complex epithelia, such as the skin. In this study, we analyzed the distribution of mouse type I keratin 16 during skin morphogenesis, in the adult hair cycle, and in challenged epidermis. In mature hair follicles, we find keratin 16 along with its type II keratin partner keratin 6 in the companion layer of the outer root sheath during anagen and in the club hair sheath during catagen and telogen. During embryonic development, the distribution of keratin 16 is uncoupled from its presumed polymerization partner, keratin 6. Keratin 16 initially localizes within early hair germs, but rapidly shifts to a subset of cells at the interface of basal and suprabasal cells above and around the hair germ. The presence of keratin 16 at the transition between mitotically active and differentiating cells is recapitulated in primary keratinocytes cultured in vitro and in phorbol 12-myristate 13-acetate-treated back skin in vivo. We propose that keratin 16 marks cells in an intermediate state of cellular properties in which keratinocytes retain the flexibility required for activities such as cell migration and even mitosis but are resilient enough to provide the structural integrity required of the early suprabasal layers in the context of development, adult hair cycling, and wound repair.
皮肤上皮的形态发生和成年毛囊的周期性循环都需要上皮细胞与下方间充质之间的整合信号。由于其独特的调控方式，角蛋白中间丝是分析复杂上皮（如皮肤）中决定和分化过程的有用标记物。在本研究中，我们分析了小鼠I型角蛋白16在皮肤形态发生、成年毛发周期以及受刺激表皮中的分布情况。在成熟毛囊中，我们发现在生长期，角蛋白16与其II型角蛋白伴侣角蛋白6一起存在于外根鞘的陪伴层中；在退行期和休止期，则存在于毛球鞘中。在胚胎发育过程中，角蛋白16的分布与其假定的聚合伴侣角蛋白6解偶联。角蛋白16最初定位于早期毛胚内，但迅速转移到毛胚上方和周围基底细胞与基底上层细胞界面处的一部分细胞中。在体外培养的原代角质形成细胞以及体内佛波酯12 -肉豆蔻酸酯13 -乙酸酯处理的背部皮肤中，有丝分裂活跃细胞与分化细胞之间的过渡处也存在角蛋白16。我们提出，角蛋白16标记处于细胞特性中间状态的细胞，在这种状态下，角质形成细胞保留了细胞迁移甚至有丝分裂等活动所需的灵活性，但又具有足够的弹性，能够在发育、成年毛发周期和伤口修复的背景下提供早期基底上层所需的结构完整性。
