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Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor.

Meyer-Hoffert U, Wu Z, Schröder JM - PLoS ONE (2009)

Bottom Line: Recombinant LEKTI-2 inhibited KLK5 but not KLK7, 14 or other serine proteases tested including trypsin, plasmin and thrombin.LEKTI-2 immune-expression was focally localized at the stratum granulosum and stratum corneum at palmar and plantar sites in close localization to KLK5.At sites of plantar hyperkeratosis, LEKTI-2 expression was increased.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

ABSTRACT
Kallikreins-related peptidases (KLKs) are serine proteases and have been implicated in the desquamation process of the skin. Their activity is tightly controlled by epidermal protease inhibitors like the lympho-epithelial Kazal-type inhibitor (LEKTI). Defects of the LEKTI-encoding gene serine protease inhibitor Kazal type (Spink)5 lead to the absence of LEKTI and result in the genodermatose Netherton syndrome, which mimics the common skin disease atopic dermatitis. Since many KLKs are expressed in human skin with KLK5 being considered as one of the most important KLKs in skin desquamation, we proposed that more inhibitors are present in human skin. Herein, we purified from human stratum corneum by HPLC techniques a new KLK5-inhibiting peptide encoded by a member of the Spink family, designated as Spink9 located on chromosome 5p33.1. This peptide is highly homologous to LEKTI and was termed LEKTI-2. Recombinant LEKTI-2 inhibited KLK5 but not KLK7, 14 or other serine proteases tested including trypsin, plasmin and thrombin. Spink9 mRNA expression was detected in human skin samples and in cultured keratinocytes. LEKTI-2 immune-expression was focally localized at the stratum granulosum and stratum corneum at palmar and plantar sites in close localization to KLK5. At sites of plantar hyperkeratosis, LEKTI-2 expression was increased. We suggest that LEKTI-2 contributes to the regulation of the desquamation process in human skin by specifically inhibiting KLK5.

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Related in: MedlinePlus

LEKTI-2 is highly expressed at sites of hyperkeratosis.Immunohistochemical staining (Vector red) of LEKTI-2 of a paraffin-embedded section of a clavus. Notice the enormously enlarged stratum corneum (hyperkeratosis) in the upper two third of the picture with a sweat gland sectioned at the upper first third. Clefts between the stratum corneum and the stratum granulosum are artefacts derived from histology processing. The upper part of the living epidermis, the stratum granulosum, exhibits a massive increase in LEKTI-2 immunoreactivity (red). A representative result out of three different samples of clavi is shown.
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pone-0004372-g008: LEKTI-2 is highly expressed at sites of hyperkeratosis.Immunohistochemical staining (Vector red) of LEKTI-2 of a paraffin-embedded section of a clavus. Notice the enormously enlarged stratum corneum (hyperkeratosis) in the upper two third of the picture with a sweat gland sectioned at the upper first third. Clefts between the stratum corneum and the stratum granulosum are artefacts derived from histology processing. The upper part of the living epidermis, the stratum granulosum, exhibits a massive increase in LEKTI-2 immunoreactivity (red). A representative result out of three different samples of clavi is shown.

Mentions: Hyperkeratosis at the palmar sites can occur due to increased local mechanical pressure and lead to hyperkeratosis in the form of clavus. Interestingly, LEKTI-2 immunoreactivity was shown to be markedly induced at lesions of clavi (Fig. 8). Since KLK5 is one of the major proteases for desquamation, increased LEKTI-2 expression at the sites of clavi might contribute to the hyperkeratosis of these lesions.


Identification of lympho-epithelial Kazal-type inhibitor 2 in human skin as a kallikrein-related peptidase 5-specific protease inhibitor.

Meyer-Hoffert U, Wu Z, Schröder JM - PLoS ONE (2009)

LEKTI-2 is highly expressed at sites of hyperkeratosis.Immunohistochemical staining (Vector red) of LEKTI-2 of a paraffin-embedded section of a clavus. Notice the enormously enlarged stratum corneum (hyperkeratosis) in the upper two third of the picture with a sweat gland sectioned at the upper first third. Clefts between the stratum corneum and the stratum granulosum are artefacts derived from histology processing. The upper part of the living epidermis, the stratum granulosum, exhibits a massive increase in LEKTI-2 immunoreactivity (red). A representative result out of three different samples of clavi is shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2631147&req=5

pone-0004372-g008: LEKTI-2 is highly expressed at sites of hyperkeratosis.Immunohistochemical staining (Vector red) of LEKTI-2 of a paraffin-embedded section of a clavus. Notice the enormously enlarged stratum corneum (hyperkeratosis) in the upper two third of the picture with a sweat gland sectioned at the upper first third. Clefts between the stratum corneum and the stratum granulosum are artefacts derived from histology processing. The upper part of the living epidermis, the stratum granulosum, exhibits a massive increase in LEKTI-2 immunoreactivity (red). A representative result out of three different samples of clavi is shown.
Mentions: Hyperkeratosis at the palmar sites can occur due to increased local mechanical pressure and lead to hyperkeratosis in the form of clavus. Interestingly, LEKTI-2 immunoreactivity was shown to be markedly induced at lesions of clavi (Fig. 8). Since KLK5 is one of the major proteases for desquamation, increased LEKTI-2 expression at the sites of clavi might contribute to the hyperkeratosis of these lesions.

Bottom Line: Recombinant LEKTI-2 inhibited KLK5 but not KLK7, 14 or other serine proteases tested including trypsin, plasmin and thrombin.LEKTI-2 immune-expression was focally localized at the stratum granulosum and stratum corneum at palmar and plantar sites in close localization to KLK5.At sites of plantar hyperkeratosis, LEKTI-2 expression was increased.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

ABSTRACT
Kallikreins-related peptidases (KLKs) are serine proteases and have been implicated in the desquamation process of the skin. Their activity is tightly controlled by epidermal protease inhibitors like the lympho-epithelial Kazal-type inhibitor (LEKTI). Defects of the LEKTI-encoding gene serine protease inhibitor Kazal type (Spink)5 lead to the absence of LEKTI and result in the genodermatose Netherton syndrome, which mimics the common skin disease atopic dermatitis. Since many KLKs are expressed in human skin with KLK5 being considered as one of the most important KLKs in skin desquamation, we proposed that more inhibitors are present in human skin. Herein, we purified from human stratum corneum by HPLC techniques a new KLK5-inhibiting peptide encoded by a member of the Spink family, designated as Spink9 located on chromosome 5p33.1. This peptide is highly homologous to LEKTI and was termed LEKTI-2. Recombinant LEKTI-2 inhibited KLK5 but not KLK7, 14 or other serine proteases tested including trypsin, plasmin and thrombin. Spink9 mRNA expression was detected in human skin samples and in cultured keratinocytes. LEKTI-2 immune-expression was focally localized at the stratum granulosum and stratum corneum at palmar and plantar sites in close localization to KLK5. At sites of plantar hyperkeratosis, LEKTI-2 expression was increased. We suggest that LEKTI-2 contributes to the regulation of the desquamation process in human skin by specifically inhibiting KLK5.

Show MeSH
Related in: MedlinePlus