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Analysis of cellular molecules associated with keratinocyte differentiation

与角质形成细胞分化相关的细胞分子分析

基本信息

批准号：
14570794
负责人：
YAMAMOTO Akemi
金额：
$ 2.24万
依托单位：
Asahikawa Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2005
项目状态：
已结题

项目摘要

We studied peptidylarginine deiminases (PADs) expression in human epidermis (Cell Mol Life Sci 2005). We found that PAD1,2 and 3 are expressed. PAD1 and PAD3 are co-localized with filaggrin. PAD was present up to the supper corneocytes where it deiminates keratin K1.We have shown that LEKI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum in the epidermis (J Invest Dermatol 2005).We also disclosed that in Netherton syndrome where LEKTI is absent, an abnormal split was seen in the superficial stratum granulosum, suggesting that LEKTI is preventing premature loss of stratum corneum cohesion.We generated SPINK5-deficient mice as a model for Netherton syndrome. Using this model, we showed that desmosome cleavage due to desmoglein 1 degradation is the primary pathogenic event in this disease. (Nature Genetics 2005).We describe a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK syndrome) caused by a mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking (Am J Hum Genet 2005). In the ichthyotic patient skin, secretion of lamellar granule proteins was inhibited.We have identified novel members of lamellar granule proteins, namely A2ML (alpha-2 macroglobulin-like) and Dermokin (J Biol Chem, 2006,J Invest Dermatol 2006).

我们研究了人表皮中肽基精氨酸脱亚胺酶（PAD）的表达（Cell Mol Life Sci 2005）。我们发现PAD 1、2和3表达。PAD 1和PAD 3与聚丝蛋白共定位。PAD存在于角质形成细胞的上层，在那里它将角蛋白K1脱亚氨基化。我们已经证明LEKI定位于与KLK 5和KLK 7分离的板层颗粒中，并分泌于表皮浅层颗粒层的细胞外间隙中（J Invest Dermatol 2005）。我们还披露，在LEKTI缺失的内瑟顿综合征中，在浅表颗粒层中观察到异常分裂，提示LEKTI可以预防角质层凝聚力的过早丧失。我们建立了SPINK 5缺陷小鼠作为内瑟顿综合征的模型。使用这个模型，我们表明，桥粒分裂由于桥粒芯蛋白1降解是在这种疾病的主要致病事件。我们描述了一种新的神经皮肤综合征，其特征在于由编码参与细胞内运输的SNARE蛋白的SNAP 29中的突变引起的脑发育不全、神经病、鱼鳞病和角化病（CEDNIK综合征）（Am J Genet 2005）。我们已经鉴定了板层颗粒蛋白的新成员，即A2 ML（α-2巨球蛋白样）和Dermokin（J Biol Chem，2006，J Invest Dermatol 2006）。