Cheng Tsing, van Vlijmen-Willems Ivonne M J J, Hitomi Kiyotaka, Pasch Marcel C, van Erp Piet E J, Schalkwijk Joost, Zeeuwen Patrick L J M
Department of Dermatology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
J Invest Dermatol. 2009 May;129(5):1232-42. doi: 10.1038/jid.2008.353. Epub 2008 Nov 13.
The cysteine protease inhibitor cystatin M/E is a key regulator of a biochemical pathway that leads to epidermal terminal differentiation by inhibition of its target proteases cathepsin L, cathepsin V, and legumain. Inhibition of cathepsin L is important in the cornification process of the skin, as we have recently demonstrated that cathepsin L is the elusive processing and activating protease for transglutaminase 3, an enzyme that is responsible for crosslinking of structural proteins in cornified envelope formation. Here, we study the localization of all players of this pathway in the human hair follicle and nail unit in order to elucidate their possible role in the biology of these epidermal appendages. We found that cathepsin L and transglutaminase 3 specifically colocalize in the hair bulb and the nail matrix, the regions that provide cells that terminally differentiate to the hair fiber and the nail plate, respectively. Furthermore, transglutaminase 3 also colocalizes with the structural proteins loricrin and involucrin, which are established transglutaminase substrates. These findings suggest that cathepsin L and transglutaminase 3 could be involved in the pathway that leads to terminal differentiation, not only in the epidermis but also in the human hair follicle and nail unit.
半胱氨酸蛋白酶抑制剂胱抑素M/E是一条生化途径的关键调节因子，该途径通过抑制其靶蛋白酶组织蛋白酶L、组织蛋白酶V和天冬酰胺内肽酶来导致表皮终末分化。我们最近证明组织蛋白酶L是转谷氨酰胺酶3难以捉摸的加工和激活蛋白酶，转谷氨酰胺酶3负责在角质包膜形成过程中交联结构蛋白，因此抑制组织蛋白酶L在皮肤的角质化过程中很重要。在此，我们研究该途径所有参与者在人毛囊和甲单位中的定位，以阐明它们在这些表皮附属器生物学中的可能作用。我们发现组织蛋白酶L和转谷氨酰胺酶3在毛球和甲母质中特异性共定位，这两个区域分别为毛发纤维和甲板提供终末分化的细胞。此外，转谷氨酰胺酶3还与结构蛋白兜甲蛋白和内披蛋白共定位，这两种蛋白是公认的转谷氨酰胺酶底物。这些发现表明，组织蛋白酶L和转谷氨酰胺酶3可能参与导致终末分化的途径，不仅在表皮中，而且在人毛囊和甲单位中。
