Bowden P E, Hainey S D, Parker G, Jones D O, Zimonjic D, Popescu N, Hodgins M B
Department of Dermatology, UWCM, Cardiff, UK.
J Invest Dermatol. 1998 Feb;110(2):158-64. doi: 10.1046/j.1523-1747.1998.00097.x.
During anagen, cell proliferation in the germinative matrix of the hair follicle gives rise to the fiber and inner root sheath. The hair fiber is constructed from structural proteins belonging to four multigene families: keratin intermediate filaments, high-sulfur matrix proteins, ultra high-sulfur matrix proteins, and high glycine-tyrosine proteins. Several hair-specific keratin intermediate filament proteins have been characterized, and all have relatively cysteine-rich N- and C-terminal domains, a specialization that allows extensive disulfide cross-linking to matrix proteins. We have cloned two complete type II hair-specific keratin genes (ghHb1 and ghHb6). Both genes have nine exons and eight introns spanning about 7 kb and lying about 10 kb apart. The structure of both genes is highly conserved in the regions that encode the central rod domain but differs considerably in the C-terminal coding and noncoding sequences, although some conservation of introns does exist. These genes have been localized to the type II keratin cluster on chromosome 12q13 by fluorescence in situ hybridization. They, and their type I partner ghHa1, are expressed in differentiating hair cortical cells during anagen. In cultured follicles, ghHa1 expression declined in cortical cells and was no longer visible after 6 d, whereas the basal epidermal keratin hK14 appeared in the regressing matrix. The transition from anagen to telogen is marked by downregulation of hair cortical specific keratins and the appearance of hK14 in the epithelial sac to which the telogen hair fiber is anchored. Further studies of the regulation of these genes will improve our understanding of the cyclical molecular changes that occur as the hair follicle grows, regresses, and rests.
在生长期，毛囊生发基质中的细胞增殖产生毛发纤维和内根鞘。毛发纤维由属于四个多基因家族的结构蛋白构成：角蛋白中间丝、高硫基质蛋白、超高硫基质蛋白和高甘氨酸 - 酪氨酸蛋白。几种毛发特异性角蛋白中间丝蛋白已得到表征，它们都具有相对富含半胱氨酸的N端和C端结构域，这种特殊结构允许与基质蛋白进行广泛的二硫键交联。我们克隆了两个完整的II型毛发特异性角蛋白基因（ghHb1和ghHb6）。这两个基因都有九个外显子和八个内含子，跨度约7kb，相距约10kb。这两个基因在编码中央杆状结构域的区域结构高度保守，但在C端编码和非编码序列上有很大差异，不过内含子也存在一些保守性。通过荧光原位杂交，这些基因已定位到12q13染色体上的II型角蛋白簇。它们以及它们的I型伴侣ghHa1在生长期分化的毛发皮质细胞中表达。在培养的毛囊中，ghHa1在皮质细胞中的表达下降，6天后不再可见，而基底表皮角蛋白hK14出现在退行的基质中。从生长期到休止期的转变以毛发皮质特异性角蛋白的下调以及休止期毛发纤维所锚定的上皮囊中hK14的出现为标志。对这些基因调控的进一步研究将增进我们对毛囊生长、退行和休止过程中发生的周期性分子变化的理解。
