Keratin 15 expression in stratified epithelia: Downregulation in activated keratinocytes

Keratin 15 expression in stratified epithelia: Downregulation in activated keratinocytes
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DOI:
10.1046/j.1523-1747.1999.00535.x
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发表时间:
1999-03-01
影响因子:
6.5
通讯作者:
Leigh, IM
Leigh, IM
中科院分区:
医学1区
文献类型:
--
作者:
Waseem, A;Dogan, B;Leigh, IM

文献摘要

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角蛋白15(K15)是一种没有确定的II型伴侣的I型角蛋白,其在表皮疾病中的表达尚未研究。在这项研究中,我们使用了LHK 15,一种针对K15多肽的最后17个氨基酸的单克隆抗体,以表明K15主要在分层组织的基底角质形成细胞中表达,包括胎儿表皮和胎儿指甲。虽然正常毛囊中的K15几乎不存在于毛球中,但它由外根鞘中的角质形成细胞亚群表达。相比之下,K14的表达被发现在整个毛囊的外根鞘;然而,当两个K14等位基因被自然消融时,K15的表达也被观察到在整个毛囊的外根鞘。K15 mRNA的表达通过原位杂交进行了评估,并证实了免疫染色的数据。K15 mRNA和蛋白表达的增加,毛囊从K14消融表皮表明上调K15基因的K14蛋白的情况下。在分化中的角质形成细胞表达活化表型的标志物的器官型培养物中,K6和K16,K15的表达未检测到。在银屑病和增生性瘢痕这两种过度增生的情况下,K15 mRNA和蛋白的表达也下调。由于银屑病和增生性瘢痕中的角质形成细胞被激活,我们得出结论,K15表达与角质形成细胞活化不相容,K15基因下调以维持活化的表型。
Keratin 15 (K15) is a type I keratin without a defined type II partner whose expression in epidermal diseases has not been investigated. In this study we have used LHK15, a monoclonal antibody raised against the last 17 amino acids of the K15 polypeptide, to show that K15 is expressed primarily in the basal keratinocytes of stratified tissues, including the fetal epidermis and fetal nail. Although K15 in normal hair follicles was virtually absent from hair bulbs, it was expressed by a subset of keratinocytes in the outer root sheath. By comparison, K14 expression was found throughout the outer root sheath of hair follicles; however, when both K14 alleles were naturally ablated, the expression of K15 was also observed throughout the outer root sheath of the follicles. Expression of K15 mRNA was assessed by in situ hybridization and corroborated the data from immunostaining. An increase in K15 mRNA and protein expression in hair follicles from the K14 ablated epidermis suggested an upregulation of the K15 gene in the absence of the K14 protein. In organotypical cultures where differentiating keratinocytes expressed markers of activated phenotype, i.e., K6 and K16, expression of K15 was undetectable. The expression of K15 mRNA and protein was also downregulated in two hyperproliferating situations, psoriasis and hypertrophic scars. Because keratinocytes in psoriasis and hypertrophic scars are activated, we conclude that K15 expression is not compatible with keratinocyte activation and the K15 gene is downregulated to maintain the activated phenotype.