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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精氨酸脱亚胺酶（PADs）的表达（Cell Mol Life Sci 2005）。我们发现PAD1,2和3表达。PAD1和PAD3与聚丝蛋白共定位。PAD存在于晚餐角质细胞，在那里它消除角蛋白K1。我们已经证明LEKI定位于板层颗粒中，与KLK5和KLK7分离，并在表皮浅层颗粒的细胞外间隙分泌（J Invest Dermatol 2005）。我们还发现，在缺乏LEKTI的内德顿综合征中，在浅层颗粒中可以看到异常分裂，这表明LEKTI可以防止角质层粘连的过早丧失。我们制造了spink5缺陷小鼠作为内瑟顿综合征的模型。通过该模型，我们发现由桥粒蛋白1降解引起的桥粒分裂是该疾病的主要致病事件。（Nature Genetics, 2005）。我们描述了一种新的神经皮肤综合征，其特征是大脑发育不良、神经病变、鱼鳞病和角膜炎（CEDNIK综合征），由SNAP29突变引起，编码参与细胞内运输的SNARE蛋白（Am J Hum Genet 2005）。在鱼鳞病患者皮肤中，板层颗粒蛋白的分泌受到抑制。我们已经确定了板层颗粒蛋白的新成员，即A2ML （α -2巨球蛋白样蛋白）和Dermokin （J Biol Chem, 2006,J Invest Dermatol 2006）。