A Study On Cathepsin C Expression In Mouse And Human Tissues

BackgroundCathepsins are lysosomal peptidases which are widely presented in varies tissues,which are play an important role in physiological activities. Cathepsins express in specific tissues and vary in different cells, or even the same cell in a different physiological environment. According to their catalytic center, cathepsins can be divided into three classes: cysteine proteases(cathepsin B, C, L, H, S, etc.), serine proteases(A and cathepsin G), and aspartic proteases(cathepsin D and E). So far, although more than 10 kinds of cathepsins have been found, their functions are unclear yet. Cathepsin C is one of them. It also known as dipeptidyl peptidase I(DPPI), is a lysosomal cysteine protease. Studies have shown that cathepsin C is highly expressed in inflammatory cells, and may be related activation of enzyme granule. In addition, although cathepsin C is detected in many tissues, but its expression location and functions are still unclear.By means of genetic testing, Toomes et al. 1999 confirmed that cathepsin C gene(CTSC) mutation can lead to a hereditary disease- palmoplantar keratosis syndrome(PLS), which is characterized as early-onset periodontitis accompanied by excessive skin keratosis, and / or purulent dermatitis, liver, lung abscess. PLS was first reported by Papillon and Lefèvre in 1924, the prevalence rate is about one to four in a million. So far, lots of studies found many different cathepsin C mutation sites in PLS patients, as well as in patients with other diseases, such as Haim-Munk syndrome(HMS) and prepubertal periodontitis(PP), which present symptoms as early onset periodontitis and / or excessive skin keratosis.As for Clinical manifestation, such diseases are mainly concentrated in an organ or tissue of inner or outer surface- gums and skin, so we hypothesized that cathepsin C may be associated with epithelial cell function. The mutations of CTSC may influence epithelial cell function, lead to local defenses drop of gums and skin, and finally lead to diseases. In order to confirm our hypothesis, we observe the expression of cathepsin C in healthy mouse organ epithelial tissue, trauma/infection mouse skin, as well as chronic periodontitis and a variety of oral mucosal disease tissues, for further study of the biological function of cathepsin C provides morphological evidence.In addition, in order to explore the relationship between the expressions of cathepsin C change and immune function of epithelial cells, we also tested the expressions of Toll-like receptor 4 in order to provide a reference for further study. AimStudy the expressions of cathepsin C in tissues of healthy mice, mice trauma/infection model and in human periodontitis and oral mucosal diseases, to serve the further study of the function, mechanisms and significance of cathepsin C in physiological and pathological processes. MethodExperiment 1: Cathepsin C expression in varies tissues in healthy mouse Cathepsin C expressions were detected by immunohistochemistry in liver, lung, intestine, bladder, buccal mucosa, gums, feet skin, and back skin tissues of healthy C57 mouse.Experiment 2: Cathepsin C expression in skin trauma /infection model in mouse C57 mice were randomly divided into three groups: normal group; 12 h, 24 h, 48 h trauma group; and 12 h, 24 h, 48 h infection group. After the skin trauma/infection model was established, the expression of Cathepsin C was observed by HE dyeing and immunohistochemical staining technique.Experiment 3: Cathepsin C expression in periodontitis and oral mucosal deseases in humam Cathepsin C and Toll-like receptor 4 expressions were detected by immunohistochemistry in chronic periodontitis, oral lichen planus, discoid lupus erythematosus, leukoplakia and squamous cell carcinoma in human. ResultsExperiment 1: Significant Cathepsin C immunoreactivities were detected in mouse liver, lung, intestine and bladder tissues, and slight or negative expression in buccal mucous membranes, gingival, back skin and paw skin.Experiment 2: Immunohistochemical staining showed: cathepsin C expression in control group is not obvious, and expression in two experience groups are obvious. Positive staining was found both in epithelial and connective tissues, and mainly located in the basal and spinous layer cells, and inflammatory cells. In addition, the staining intensity of cathepsin C in two experience groups increase by the experimental time, and staining intensity of infection group is slightly higher than trauma group.Experiment 3: The expression of Cathepsin C in chronic periodontitis, oral lichen planus, discoid lupus, leukoplakia and squamous cell carcinoma have a certain consistency with that of TLR4, and they are expressed in epithelial or connective tissue. ConclusionCathepsin C expression in different organs of mice in different epithelium, suggesting that it has a role in maintaining normal physiological function of epithelial cells. Unregulated of Cathepsin C in the trauma/ infection mouse skin, suggesting Cathepsin C may be involved in the proliferation and differentiation of epithelial cells, and local immune defense. Expression of Cathepsin C in periodontitis and oral mucosa diseases, suggesting that it may related immune function of epithelial cells.