Expression of Cathepsin K in Lung Epithelial Cells

Abstract

Alveolar and bronchial epithelial cells have been shown to have regulatory functions in the maintenance of lung structure and function. Recent evidence supports the premise that these cells can synthesize a variety of extracellular matrix components in vitro, suggesting an active participation in connective tissue remodeling. Their possible role in extracellular matrix degradation, however, is less clear. This study addresses the question of whether alveolar and bronchial epithelial cells express the highly collagenolytic and elastinolytic cysteine proteinase cathepsin K, which has recently been newly described. We provide evidence that the epithelial cell lines A549 and BEAS-2B are capable of expressing cathepsin K messenger RNA. Furthermore, we show that cathepsin K is expressed in normal bronchial epithelial cells. Western blot analyses of human lung-tissue lysates revealed specific immunoreactivity at molecular weights of 46 and 27 kD, corresponding to the procathepsin and the mature cathepsin K. Immunohistochemical analyses showed a pronounced staining of bronchial epithelial cells and in single alveolar epithelial cells. Using a specific fluorogenic cytochemical assay, the intracellular activity of the enzyme was localized. These findings demonstrate that bronchial and alveolar epithelial cells are capable of expressing cathepsin K, which could be of considerable importance for remodeling processes of the extracellular matrix in the lung.

Regulation of TGF-β1-driven Differentiation of Human Lung Fibroblasts

“…Conversely to that observed for CCD-19Lu myofibroblasts, we detected Cat activity in IPF culture media. This residual proteolytic activity of IPF samples obtained from lung biopsies probably relied on the presence (in addition to fibroblastic cells) of some resident macrophages and epithelial cells that are the primary source of extracellular Cats (8,22,58,59). Nevertheless, as observed for the CCD-19Lu model, inhibition of cystatin C by siRNA drastically rescued (4 -5-fold) Cat B activity (p Ͻ 0.001) (Fig.…”

Down‐regulation of cathepsin K in synovium leads to progression of osteoarthritis in rabbits

“…The cathepsin K gene was considered to be exclusively expressed in osteoclasts. Recently, however, this gene was identified in various types of cells, including mononuclear cells, that may act as precursor cells for osteoclasts (26), macrophages (27), and epithelial cells (28)(29)(30)(31). Cathepsin K has been considered to be a key enzyme involved in the degradation of articular cartilage, at least in the advanced and/or end stages of OA.…”

Analysis of Host- and Tumor-Derived Proteinases Using a Custom Dual Species Microarray Reveals a Protective Role for Stromal Matrix Metalloproteinase-12 in Non–Small Cell Lung Cancer

“…Cathepsin K RNA levels have been reported to be higher in human lung tumors compared with normal lung by RT-PCR analysis (23). Cathepsin K is capable of degrading components of the ECM, including collagen type I, II, and IV, as well as elastin at neutral pH (24). Cathepsin K expression is found in the fibroblasts of patients with fibrotic lungs, and experiments in cathepsin K-null mice revealed that cathepsin K can prevent lung fibrosis in bleomycin-treated mice by contributing to ECM turnover (25).…”