Abstract
Kallikrein-related peptidases (KLKs) and the lymphoepitherial azal-type inhibitor (LEKTI) play important roles in corneocyte esquamation. It is suggested that KLKs such as KLK5 and 7 are eleased from LEKTI because of acidic pH at the skin surface and egrades corneodesmosomes, resulting in the removal of surface orneocytes. It is still obscure whether the KLK-LEKTI interacion is easily broke in such a weak acidic pH(5.5-6.5). Recently e reported cloning of a new PRSS3 gene product, keratinocytepecificmesotrypsin from the cDNA library. The aim of this study is o elucidate involvementof PRSS3 in thedesquamationprocess.We onstructed various recombinant LEKTI proteins, D2, D2-5, D2-6, 2-7, D5, D6, D6-9, D7, D7-9 andD10-15. All of these recombinants nhibited KLK5 with different extent. However, they did not show ny inhibitory effect on PRSS3. Interestingly we found that single omain LEKTI, D5 and D6were degraded by PRSS3. We then invesigated pH susceptibility between KLK5 and each LEKTI domain. LK5 was incubated with D5, or D6 in different pH buffers ranging rom pH 3.5 to pH 9.0 and residual activities were measured using ln-Ala-Arg-MCA. KLK5 was active between pH 5.5 to pH 9 and hat D5 as well as D6 completely suppressed KLK5 activity in the amepH range. Other LEKTI domain constructs gave similar results. n order to elucidate whether PRSS3 could participate in desquaation process, localization in human skin was examined with mmunoelectronmicroscopy. PRSS3was localized in the cytoplasm f granular cells and intercellular spaces of the cornified layer. Colectively our results suggest that PRSS3 is actively involved in the esquamation process via degradation of the intrinsic inhibitor, EKTI.
Published Version
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