LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum
LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum
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DOI：
10.1111/j.0022-202x.2004.23583.x
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发表时间：
2005-02-01
影响因子：
6.5
通讯作者：
Hovnanian, A
中科院分区：
文献类型：
--
作者：
Ishida-Yamamoto, A;Deraison, C;Hovnanian, A
淋巴上皮型Kazal相关抑制物(LEKTI)是由丝氨酸蛋白酶抑制物Kazal-type 5(SPINK5)编码的一种可能的丝氨酸蛋白酶抑制物。在正常皮肤中，它在分化的角质形成细胞中强烈表达，但在Netherton综合征(NS)中表达显著减少或缺失，NS是一种由SPINK5突变引起的严重鱼鳞病。然而，目前，lekti在细胞内的准确定位和生物学作用尚不清楚。为了了解lekti的功能作用，我们用激光共聚焦扫描显微镜和免疫电子显微镜研究了lekti的可能靶点--lekti与激肽释放酶(KLK)7和KLK5在人表皮中的定位。在正常皮肤中，Lekti、KLK7和KLK5均存在于板层颗粒(LG)系统中，但各有分布。Lekti的表达早于KLK7和KLK5。NS皮肤无LEKTI，4例中3例可见浅层颗粒层异常裂开。总之，这些结果表明，在正常皮肤中，LG系统比KLK7和KLK5更早地运输和分泌lekti，防止角质层完整性/凝聚力的过早丧失。我们的数据为LG的生物学功能和NS的发病机制提供了新的见解。
Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a putative serine protease inhibitor encoded by serine protease inhibitor Kazal-type 5 (SPINK5). It is strongly expressed in differentiated keratinocytes in normal skin but expression is markedly reduced or absent in Netherton syndrome (NS), a severe ichthyosis caused by SPINK5 mutations. At present, however, both the precise intracellular localization and biological roles of LEKTI are not known. To understand the functional role of LEKTI, we examined the localization of LEKTI together with kallikrein (KLK)7 and KLK5, possible targets of LEKTI, in the human epidermis, by confocal laser scanning microscopy and immunoelectron microscopy. In normal skin, LEKTI, KLK7, and KLK5 were all found in the lamellar granule (LG) system, but were separately localized. LEKTI was expressed earlier than KLK7 and KLK5. In NS skin, LEKTI was absent and an abnormal split in the superficial stratum granulosum was seen in three of four cases. Collectively, these results suggest that in normal skin the LG system transports and secretes LEKTI earlier than KLK7 and KLK5 preventing premature loss of stratum corneum integrity/cohesion. Our data provide new insights into the biological functions of LG and the pathogenesis of NS.