For healthy people, the most common skin problem is the occurrence of visible scales on the skin surface. This phenomenon is commonly seen on dry skin. Many morphological and biochemical studies on the stratum corneum have revealed the aspects of skin. However, we still do not know why and how scales appear on the skin surface, except that a defect of the desquamation process in the stratum corneum must be involved. In this study, we examined the mechanism of desquamation, to establish what factors influence the mechanism and what treatments might be effective for skin care. We found two types of proteases, trypsin type (30kDa) and chymotrypsin type (25kDa), in stratum corneum (SC). cDNA cloning followed by nucleotide sequence analysis revealed that the chymotrypsin-like protease corresponded to the reported chymotrypsin-like enzyme in stratum corneum (SCCE). Trypsin-like protease corresponded to trypsinogen IV and we found new type of trypsinogen. Desmosomes in SC sheets were digested and SC sheets were dissociated into individual intact cells in buffer solution, whereas heat-treatment or addition of inhibitors of these proteases to the buffer solution prevented the degradation of desmosomes and the cell dissociation. Leupeptin or chymostatin retarded the cell dissociation only about half as effectively as aprotinin, but a mixture of the two inhibited stratum corneum sheet degradation as potently as aprotinin. These results support the hypothesis that desmosomes play a key role in the adheasion of SC cells, and the digestion of desmosomes by these two types of serine proteases leads to SC desquamation. An age-related decrease in the activity of the trypsin-type protease was observed in normal subjects. Digestion of desmosomes in SC by the proteases was influenced by the water content in SC. Lower humidity (lower water content in stratum corneum) resulted in a decrease of desmosomal degradation. Our studies demonstrated that desquamation was influenced by two factors. One is water content in the stratum corneum. Under the low water condition enzymes cannot work well, even if the contents of the enzymes are normal. In this case, humectant treatment was effective by supplying water to the stratum corneum. The other factor is a decline in the activity of the proteases themselves. This can be seen in diseased or aged skin. Humectant treatment is not sufficient in this case, compounds that accelerate desmosomal digestion independently of the water content in the stratum corneum is required. Derivatives of dicarboxylic acid are thought to be the candidate for such ingreadents.
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