The role of two endogenous proteases of the stratum corneum in degradation of desmoglein-1 and their reduced activity in the skin of ichthyotic patients

Abstract

We investigated the role of stratum corneum (SC) trypsin-like and chymotrypsin-like serine proteases in the degradation of desmoglein-1 (DSG-1) in the SC sheet. DSG-1, whose presence in the SC sheet was confirmed by Western blot analysis, was degraded completely during incubation of the SC sheet in Tris buffer. The degradation of DSG-1 was inhibited by the addition of protease inhibitors, such as aprotinin or a mixture of leupeptin and chymostatin. Either leupeptin or chymostatin alone did not inhibit its degradation. These results indicated that both trypsin-like and chymotrypsin-like serine proteases are involved in the degradation of DSG-1. We further examined the activities of the two proteases in the SC obtained from patients with ichthyosis vulgaris, in whom SC desquamation is abnormal. The enzymatic activities measured using synthetic substrates were significantly decreased in these ichthyotic SC samples. This result supports the idea that these proteases play an important role in normal SC desquamation.

Purification, Molecular Cloning, and Expression of a Human Stratum Corneum Trypsin-like Serine Protease with Possible Function in Desquamation

“…The function of SCTE in the skin is not known. It remains to be elucidated whether it is involved in desquamation, as has been suggested (13)(14)(15). Most likely, being a protease with trypsin-like substrate specificity, SCTE is a possible candidate for being responsible for activation of zymogens such as pro-SCCE.…”

“…The 30-kDa protease(s) can be inhibited with leupeptin, but not by chymostatin (7)(8), suggesting a trypsin-like primary substrate specificity. Suzuki et al (13)(14)(15) have presented evidence that the spontaneous dissociation of corneocytes that can be induced in stratum corneum samples is dependent upon the activity of trypsin-as well as chymotrypsin-like enzymes, and they also suggested that the trypsin-like protease involved was the 30-kDa component detected on zymograms.…”

Analysis of human kallikrein 7 expression as a potential biomarker in cervical neoplasia

“…10,[27][28][29][30][31] Several reports describe that hK7 plays an important role in the normal physiology of the skin, particularly in epidermal homeostasis, 13,14 by degrading intra-and extracellular components of the epidermis important for cellular cohesiveness and facilitating cell desquamation during the terminal stages of normal epidermal turnover. 10,[15][16][17][18][19] On the other hand, deregulated expression of hK7 is involved in skin pathologies, such psoriasis, 32 abnormal keratinization 33 and inflammatory reactions, because of its ability to activate proinflammatory cytokines, such as interleukin-1b (IL-1 b). 34,35 Almost 15 kallikrein types have been identified, and nowadays the tissue kallikreins are considered a rich source of cancer biomarkers.…”

“…13,14 Although it has been shown that this protein is involved in degradation of several components of the extracellular matrix, such as desmoglein-1, desmocollin-1, corneodesmossomes and fibronectin, its role in human malignancies remains unclear. [15][16][17][18][19] High hK7 expression (messenger RNA and/or protein level) has been observed in breast 20 and ovary tumors 21,22 and is considered an unfavorable prognostic marker for these pathologies. 10 To date, few studies have addressed hK7 expression in cervical tumors.…”

“…Current estimates indicate that $494,000 women are diagnosed with cervical cancer worldwide and almost 274,000 die from the disease every year. 1,2 It has been recognized that persistent infection with high-risk (HR) human papillomavirus (HPV) types (16,18,31,33,35,39,45, 51, 52, 56, 58, 59 and 68) is a necessary cause for the development of preinvasive and invasive cervical cancer (ICC). 3 Although HPV infection has a prevalence of about 20-40% among sexually active and cytological normal women, 93-99.7% of cervical cancers are positive for HR-HPV.…”