Table 1.
Tissue | Disease | Involvement of CatK |
---|---|---|
Bone | Pycnodysostosis (PD) | A homozygous or compound heterozygous mutation (mutations that occur on different copies of genes and may completely “knock-out” gene function) in the CatK gene 236G > A, 121–1G > A and 926T > C, causes lower degradation of type I collagen due to lack of CatK activity [94,95]. |
Postmenopausal osteoporosis (PO) | In a combination of hyper-active osteoclasts and less functional osteoblasts (typically for estrogen-deficient women), CatK inhibitors can target the resorption process [54]. | |
Osteoarthritis (OA) | The up-regulated expression of the CatK collagenase activity could affect the cartilage matrix degradation in the late stadium of osteoarthritis [96]. | |
Rheumatoid arthritis (RA) | CatK inhibition can play a significant role in cartilage degradation, retarding the bone loss process and joint destruction [97,98,99]. | |
Gaucher Disease (GD) | A multisystemic disorder, associated with progressive accumulation of Gaucher cells—large macrophages that store glucocerebroside. In GD patients elevated CatK levels are observed, which can lead to osteoporosis and lytic bone lesions [56]. | |
Skin | Psoriasis (PS) | Psoriatic lesions (an increased copy number of variations in β-defensin gene locus) express an elevated level of CatK compared to healthy skin [65]. |
Scar formation (SF) | In surgical scars compared to normal skin, is observed a proteolytic activity of CatK [57]. | |
Lung | Lung fibrosis (LF) | CatK protects against matrix deposition in bleomycin-induced LF [100]. |
Pulmonary lymphangioleiomyomatosis (PLAM) | General expression of CatK activity was observed during PLAM [101,102]. | |
Atherosclerosis (AS) | Stress-induced—CatK expression in endothelial cells can lead to vascular remodeling and atherosclerosis [103]. | |
Adipose tissue | Obesity/overweight | CatK expression can be detected in pre-adipocytes and be further up-regulated in the process of differentiation. The lack of CatK retards the adipogenesis [104,105]. |
Central nervous system | Schizophrenia | High levels of CatK in individuals suffering from schizophrenia, as a result of long-term treatment of the patients with neuroleptics [68,106]. |
Cerebral aneurysm (CA) | Cystein cathepsins cause degradation of ECM in aneurysmal wall in the late state of CA. The administration of cysteine proteases inhibitors (CPIs) leads to prevention of CA progression [67]. | |
Chronic subdural hematoma (CSH) | The expression of CatK in CSH patients, may lead to CSH development [107]. | |
Cancer | Adenocarcinoma Chondrosarcoma Renal and extrarenal perivascular epithelioid tumors (PEComas) Alveolar soft part sarcoma Basal cell carcinoma Oral tongue squamous carcinoma cells Breast and prostate cancer Other epithelial-derived cell cancers |
High levels of cathepsin K have been observed in metastatic tumors, which correlates with its primary function to degrade collagen, thus aiding tumor invasion and metastasis [82]. |