Oji V, Oji M E, Adamini N, Walker T, Aufenvenne K, Raghunath M, Traupe H
Department of Dermatology, University of Münster, Germany.
Br J Dermatol. 2006 May;154(5):860-7. doi: 10.1111/j.1365-2133.2005.07109.x.
Plasminogen activator inhibitor-2 (PAI-2), a regulatory serpin of the plasminogen activator (PA) system, has been described as a potential component of the cornified cell envelope (CE). Protease inhibitors are essential for skin homeostasis and in particular for the regulation of the desquamation process. Therefore, an aberrant expression of PAI-2 could be involved in the pathogenesis of certain cornification disorders.
Evaluation of the expression of PAI-2 in different types of congenital ichthyosis, especially in lamellar ichthyosis/nonbullous congenital ichthyosiform erythroderma (LI/NCIE) and in Netherton syndrome (NTS). Demonstration of the functional relationship between PAI-2 and transglutaminase (TGase)-1.
Using immunohistochemistry we evaluated cryosections from individuals suffering from LI/NCIE (n=67), NTS (n=6), ichthyosis-follicularis-atrichia-photophobia syndrome (n=2) and Harlequin ichthyosis (n=1) in comparison with psoriasis vulgaris and healthy skin. Moreover, we assessed the respective TGase-1 activity and the presence of TGase-1 protein. A functional assay was developed to elucidate whether PAI-2 is a substrate for TGase-1.
PAI-2 is expressed in different types of congenital ichthyosis and there is a strong correlation between TGase-1 activity and PAI-2 protein signal. Double staining revealed a strong colocalization of TGase-1 activity and PAI-2 protein. The epidermal incorporation of the specific PAI-2 peptide containing a TGase binding site revealed a strong pericellular staining in the stratum granulosum in healthy skin. In contrast, TGase-1-deficient skin showed only a lamellar staining in the stratum corneum.
We provide in vivo evidence that PAI-2 is a substrate of TGase-1. The normal expression of PAI-2 in a large group of TGase-1-proficient LI/NCIE patients makes it rather unlikely that PAI-2 alone is a primary molecular cause of LI/NCIE.
纤溶酶原激活物抑制剂-2（PAI-2）是纤溶酶原激活物（PA）系统的一种调节性丝氨酸蛋白酶抑制剂，已被描述为角质化细胞包膜（CE）的潜在组成部分。蛋白酶抑制剂对于皮肤稳态至关重要，尤其是对于脱屑过程的调节。因此，PAI-2的异常表达可能参与某些角化异常疾病的发病机制。
评估PAI-2在不同类型先天性鱼鳞病中的表达，特别是在板层状鱼鳞病/非大疱性先天性鱼鳞病样红皮病（LI/NCIE）和Netherton综合征（NTS）中的表达。证明PAI-2与转谷氨酰胺酶（TGase）-1之间的功能关系。
使用免疫组织化学方法，我们评估了LI/NCIE患者（n = 67）、NTS患者（n = 6）、鱼鳞病-毛囊角化病-无汗-畏光综合征患者（n = 2）和丑角样鱼鳞病患者（n = 1）的冰冻切片，并与寻常型银屑病和健康皮肤进行比较。此外，我们评估了各自的TGase-1活性和TGase-1蛋白的存在情况。开发了一种功能测定法以阐明PAI-2是否是TGase-1的底物。
PAI-2在不同类型的先天性鱼鳞病中表达，并且TGase-1活性与PAI-2蛋白信号之间存在很强的相关性。双重染色显示TGase-1活性和PAI-2蛋白强烈共定位。含有TGase结合位点的特异性PAI-2肽在健康皮肤颗粒层中的表皮掺入显示出强烈的细胞周围染色。相比之下，TGase-1缺陷皮肤仅在角质层中显示出板层状染色。
我们提供了体内证据表明PAI-2是TGase-1的底物。在大量TGase-1功能正常的LI/NCIE患者中PAI-2的正常表达使得PAI-2单独作为LI/NCIE的主要分子病因的可能性相当小。
