Expression and Abnormalities of Keratinocyte Terminal Differentiation-Associated Proteins

对正常表皮角化细胞包膜形成过程的免疫电子显微镜分析表明，总伞花苷比三氯环丙烷更早交联化(组织化学细胞化学，44：167-175,1996)。此外，我们还发现银屑病无颗粒层的表皮角化的细胞膜富含总环蛋白并在早期形成，而有颗粒层的银屑病表皮有与正常相似的细胞膜(J组织化学细胞化学，44：167-175,1996)。银屑病表皮可分为颗粒层和无颗粒层两种类型，形态计量学评价两者具有不同的增殖情况(BR J Dermatol 135：433-438,1996)。我们通过增加培养液中钙离子浓度的方法诱导培养的正常人角质形成细胞表达天花粉蛋白和SprR，并分析了它们的定位和超微结构的变化。结果表明，…在体外培养的正常人角质形成细胞中有表达。当我们分析角质形成细胞分化相关蛋白的表达模式时，我们发现Profilaggrin和Trichohyalin在正常和银屑病表皮、舌上皮和培养的角质形成细胞中有不同的表达模式，尽管它们具有相似的基因结构(BR J Dermatol，137：9-16,1997)。通过形态和分子遗传学研究，我们发现遗传性角化障碍、Vohwinkel综合征和进行性对称性红斑角化病是氯化蛋白的疾病(《自然遗传学》，13：70-77,1996)。J Invest Dermatol，109：604-610,1997，Am J Hum Genet，61：581-589,1997)。在对转谷氨酰胺酶1基因敲除小鼠角化细胞包膜形成、包膜前体蛋白的分布以及表皮形态和功能的分析中，发现角化细胞包膜形成以及氯丙菊酯和Profilaggrin的分布和交联性被破坏，表皮屏障功能严重降低，小鼠出生后不久死亡(PNAS，在新闻中)。较少

Immunoelectron microscopic analysis of the process of cornified cell envelope formation in normal epidermis showed that involucrin is cross-linked earlier than loricrin (J Histochem Cytochem, 44 : 167-175,1996). Furthermore, we showed that cornified cell envelopes in psoriatic epidermis without granular layr was rich in involucrin and formed in a premature stage, while psoriatic epidermis with granular layr had envelopes similar to normal (J Histochem Cytochem, 44 : 167-175,1996). We also showed that psoriatic epidermis can be classified into two types ; epidermis with granular layr and without granular layr and these two have different proliferative situation when assessed by morphometry (Br J Dermatol 135 : 433-438,1996. J Invest Dermatol, 109 : 806-810,1997).We induced expression of involucrin and SPRR in cultured normal human keratinocytes by increasing calcium concentration in the culture medium, and analyzed their localization and ultrastructural changes and showed that involucri … More n and SPRR were expressed and incorporated into the cornified cell envelopes in this order (J Invest Dermatol, 108 : 12-16,1997).When we assessed expression patterns of keratinocytes differentiation-related proteins, we found that profilaggrin and trichohyalin had distinct expression patterns in normal and psoriatic epidermis, tongue epithelia and cultured keratinocytes despite that they have similar gene structures (Br J Dermatol, 137 : 9-16,1997). We further revealed that involucrin gene expression is stimulated by alpha and eta isoforms of protein kinase C (J Invest Dermatol, in press).We showed that genetic keratinization disorders, Vohwinkel syndrome and progressive symmetric erythrokeratoderma were diseases of loricrin by morphological and molecular genetic studies (Nature Genetics, 13 : 70-77,1996. J Invest Dermatol, 109 : 604-610,1997, Am J Hum Genet, 61 : 581-589,1997) and we proposed that these diseases can be called loricrin keratoderma (Histol & Histopath, in press. Exp Dermatol, in press).In the analysis of cornified cell envelope formation, disribution of envelope precursor protein, and morphology and function of epidermis in knockout mice for the transglutaminase 1 gene, it was found that cornified cell envelope formation, and distribution and cross-linking of loricrin and profilaggrin were disrupted, barrier function of the epidermis was severely decreased and mice died soon after birth (PNAS,in press). Less