Egelrud T, Brattsand M, Kreutzmann P, Walden M, Vitzithum K, Marx U C, Forssmann W G, Mägert H J
Department of Public Health and Clinical Medicine, Dermatology and Venereology, University of Umeå, Umeå, Sweden.
Br J Dermatol. 2005 Dec;153(6):1200-3. doi: 10.1111/j.1365-2133.2005.06834.x.
Several skin diseases and atopic disorders including Netherton syndrome and atopic dermatitis have been associated with mutations and deviations of expression of SPINK5, the gene encoding the human 15-domain serine proteinase inhibitor LEKTI. The biochemical mechanisms underlying this phenomenon have not yet been fully clarified.
To identify target proteinases of LEKTI important for processes of desquamation and inflammation of the skin which will enable the development of specific drugs.
The inhibitory activities of LEKTI domains 6 and 15 were tested on a number of commercially available serine proteinases and also on the purified kallikreins hK5 and hK7. In addition, recombinant hK5 was used.
LEKTI domain 6 is a potent inhibitor of hK5 and hK7, whereas LEKTI domain 15 exhibits inhibitory activity on plasmin. hK5 and hK7 in particular are relevant to skin disorders.
The inhibition of hK5 and hK7 by LEKTI domain 6 indicates an important regulatory role of LEKTI in processes of skin desquamation and inflammation, which may explain the severe pathological symptoms associated with abnormalities of SPINK5 and/or its expression. Thus, LEKTI represents a potential drug for the treatment of these disorders.
包括 Netherton 综合征和特应性皮炎在内的几种皮肤病和特应性疾病与编码人 15 结构域丝氨酸蛋白酶抑制剂 LEKTI 的基因 SPINK5 的突变和表达偏差有关。这一现象背后的生化机制尚未完全阐明。
确定对皮肤脱屑和炎症过程重要的 LEKTI 靶蛋白酶，这将有助于开发特异性药物。
测试了 LEKTI 结构域 6 和 15 对多种市售丝氨酸蛋白酶以及纯化的激肽释放酶 hK5 和 hK7 的抑制活性。此外，还使用了重组 hK5。
LEKTI 结构域 6 是 hK5 和 hK7 的有效抑制剂，而 LEKTI 结构域 15 对纤溶酶具有抑制活性。特别是 hK5 和 hK7 与皮肤疾病相关。
LEKTI 结构域 6 对 hK5 和 hK7 的抑制表明 LEKTI 在皮肤脱屑和炎症过程中具有重要的调节作用，这可能解释了与 SPINK5 及其表达异常相关的严重病理症状。因此，LEKTI 是治疗这些疾病的潜在药物。
