Quintanilla-Dieck Maria J, Codriansky Katerine, Keady Michelle, Bhawan Jag, Rünger Thomas M
Department of Dermatology, Boston University School of Medicine, Boston, MA 02118, USA.
Exp Dermatol. 2009 Jul;18(7):596-602. doi: 10.1111/j.1600-0625.2009.00855.x. Epub 2009 Mar 12.
Cathepsin K (catK) is a lysosomal cysteine protease with strong collagenolytic activity well known to mediate bone resorption in osteoclasts. Recently, catK has also been reported to be expressed in other tissues. In the dermis, it is expressed only under certain circumstances such as scarring or inflammation. We therefore investigated the expression and regulation of this protease in dermal fibroblasts using immunoblotting and immunostaining. Cultured skin fibroblasts were found to strongly express catK in lysosomes. Internalization of collagen I and IV to lysosomes of fibroblasts indicates a role of catK in intracellular collagen degradation after endocytosis, a process that is different from the metalloproteinase-mediated collagen degradation in the extracellular space. In fibroblasts, interleukin-1alpha and cellular confluence upregulate catK expression and transforming growth factor-beta1 inhibits confluence-induced catK upregulation in skin fibroblasts. RANKL (ligand of receptor activator of NF-kappaB) did not alter catK expression. These regulators of catK expression are likely to play a role in the as-needed upregulation in certain skin conditions, where the prominent matrix-degrading properties of catK are thought to require tight regulation to maintain the homeostasis of the extracellular matrix.
组织蛋白酶K（catK）是一种溶酶体半胱氨酸蛋白酶，具有很强的胶原酶活性，众所周知它在破骨细胞介导骨吸收过程中发挥作用。最近，也有报道称catK在其他组织中表达。在真皮中，它仅在诸如瘢痕形成或炎症等特定情况下表达。因此，我们使用免疫印迹和免疫染色法研究了这种蛋白酶在真皮成纤维细胞中的表达和调控。研究发现，培养的皮肤成纤维细胞在溶酶体中强烈表达catK。I型和IV型胶原内化至成纤维细胞的溶酶体表明，catK在胞吞作用后细胞内胶原降解过程中发挥作用，这一过程不同于细胞外空间中金属蛋白酶介导的胶原降解。在成纤维细胞中，白细胞介素-1α和细胞汇合上调catK表达，而转化生长因子-β1抑制皮肤成纤维细胞中汇合诱导的catK上调。核因子κB受体激活蛋白配体（RANKL）不会改变catK表达。这些catK表达的调节因子可能在某些皮肤状况下按需上调中发挥作用，在这些状况下，catK突出的基质降解特性被认为需要严格调控以维持细胞外基质的稳态。
