Komatsu N, Saijoh K, Toyama T, Ohka R, Otsuki N, Hussack G, Takehara K, Diamandis E P
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, Canada, M5G 1X5.
Br J Dermatol. 2005 Aug;153(2):274-81. doi: 10.1111/j.1365-2133.2005.06754.x.
Human tissue kallikreins are a gene family (KLK1-KLK15) encoding for 15 secretory serine proteases (hK1-hK15). Two tissue kallikrein proteins, hK5 and hK7, were previously found in the stratum corneum (SC), stratum granulosum (SG) and appendages. hK8 was also shown to be secreted via lamellar granules and numerous KLK mRNAs were previously identified. KLKs are believed to be responsible for desquamation of corneocytes and sebum, sweat and hair maturation.
To demonstrate immunohistochemically the expression of hK6, hK8 and hK13 in normal skin tissue and to show an increased cell number expressing kallikrein mRNAs and proteins in psoriasis vulgaris (PV) and atopic dermatitis (AD).
Samples of normal, PV and AD skin were obtained. hK6-, hK8- and hK13-specific antibodies were produced and used for immunohistochemical analysis. Multiple KLK mRNAs were synthesized and used for in situ hybridization study.
Three other hKs, namely hK6, hK8 and hK13, were immunohistochemically identified as new skin serine proteases in the whole SC, SG, sebaceous glands, eccrine sweat glands, hair follicles and nerves. We also demonstrated an increased number of cells expressing KLK mRNAs and hKs in PV and AD. In PV, KLK mRNAs/hKs were predominantly expressed in the upper epidermis. In AD, hK distribution was rather diffuse and expanded into the lower epidermis.
The colocalization of various hKs seems to be essential for the regulation of serine protease activity in skin and for steady desquamation and skin barrier function. Moreover, the increased number of cells expressing multiple KLK mRNA and hK in PV and AD could be a clue to elucidate their pathogenesis.
人组织激肽释放酶是一个基因家族（KLK1 - KLK15），编码15种分泌性丝氨酸蛋白酶（hK1 - hK15）。此前在角质层（SC）、颗粒层（SG）和附属器中发现了两种组织激肽释放酶蛋白，即hK5和hK7。hK8也被证明是通过板层颗粒分泌的，并且此前已鉴定出许多KLK mRNA。激肽释放酶被认为与角质形成细胞的脱屑以及皮脂、汗液和毛发的成熟有关。
通过免疫组织化学方法证明hK6、hK8和hK13在正常皮肤组织中的表达，并显示寻常型银屑病（PV）和特应性皮炎（AD）中表达激肽释放酶mRNA和蛋白的细胞数量增加。
获取正常、PV和AD皮肤样本。制备hK6、hK8和hK13特异性抗体并用于免疫组织化学分析。合成多种KLK mRNA并用于原位杂交研究。
通过免疫组织化学方法在整个SC、SG、皮脂腺、小汗腺、毛囊和神经中鉴定出另外三种hK，即hK6、hK8和hK13，它们是新的皮肤丝氨酸蛋白酶。我们还证明了PV和AD中表达KLK mRNA和hK的细胞数量增加。在PV中，KLK mRNA/hK主要在上表皮表达。在AD中，hK的分布较为弥散并扩展至下表皮。
各种hK的共定位似乎对于皮肤中丝氨酸蛋白酶活性的调节以及稳定的脱屑和皮肤屏障功能至关重要。此外，PV和AD中表达多种KLK mRNA和hK的细胞数量增加可能是阐明其发病机制的线索。
