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Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin

The membrane-bound serine proteases prostasin and matriptase and the Kunitz-type protease inhibitors HAI-1 and HAI-2 are all expressed in human skin and may form a tightly regulated proteolysis network, contributing to skin pathophysiology. Evidence from other systems, however, suggests that the rel...

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Autores principales: Lee, Shiao-Pieng, Kao, Chen-Yu, Chang, Shun-Cheng, Chiu, Yi-Lin, Chen, Yen-Ju, Chen, Ming-Hsing G., Chang, Chun-Chia, Lin, Yu-Wen, Chiang, Chien-Ping, Wang, Jehng-Kang, Lin, Chen-Yong, Johnson, Michael D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811018/
https://www.ncbi.nlm.nih.gov/pubmed/29438412
http://dx.doi.org/10.1371/journal.pone.0192632
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author Lee, Shiao-Pieng
Kao, Chen-Yu
Chang, Shun-Cheng
Chiu, Yi-Lin
Chen, Yen-Ju
Chen, Ming-Hsing G.
Chang, Chun-Chia
Lin, Yu-Wen
Chiang, Chien-Ping
Wang, Jehng-Kang
Lin, Chen-Yong
Johnson, Michael D.
author_facet Lee, Shiao-Pieng
Kao, Chen-Yu
Chang, Shun-Cheng
Chiu, Yi-Lin
Chen, Yen-Ju
Chen, Ming-Hsing G.
Chang, Chun-Chia
Lin, Yu-Wen
Chiang, Chien-Ping
Wang, Jehng-Kang
Lin, Chen-Yong
Johnson, Michael D.
author_sort Lee, Shiao-Pieng
collection PubMed
description The membrane-bound serine proteases prostasin and matriptase and the Kunitz-type protease inhibitors HAI-1 and HAI-2 are all expressed in human skin and may form a tightly regulated proteolysis network, contributing to skin pathophysiology. Evidence from other systems, however, suggests that the relationship between matriptase and prostasin and between the proteases and the inhibitors can be context-dependent. In this study the in vivo zymogen activation and protease inhibition status of matriptase and prostasin were investigated in the human skin. Immunohistochemistry detected high levels of activated prostasin in the granular layer, but only low levels of activated matriptase restricted to the basal layer. Immunoblot analysis of foreskin lysates confirmed this in vivo zymogen activation status and further revealed that HAI-1 but not HAI-2 is the prominent inhibitor for prostasin and matriptase in skin. The zymogen activation status and location of the proteases does not support a close functional relation between matriptase and prostasin in the human skin. The limited role for HAI-2 in the inhibition of matriptase and prostasin is the result of its primarily intracellular localization in basal and spinous layer keratinocytes, which probably prevents the Kunitz inhibitor from interacting with active prostasin or matriptase. In contrast, the cell surface expression of HAI-1 in all viable epidermal layers renders it an effective regulator for matriptase and prostasin. Collectively, our study suggests the importance of tissue distribution and subcellular localization in the functional relationship between proteases and protease inhibitors.
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spelling pubmed-58110182018-02-28 Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin Lee, Shiao-Pieng Kao, Chen-Yu Chang, Shun-Cheng Chiu, Yi-Lin Chen, Yen-Ju Chen, Ming-Hsing G. Chang, Chun-Chia Lin, Yu-Wen Chiang, Chien-Ping Wang, Jehng-Kang Lin, Chen-Yong Johnson, Michael D. PLoS One Research Article The membrane-bound serine proteases prostasin and matriptase and the Kunitz-type protease inhibitors HAI-1 and HAI-2 are all expressed in human skin and may form a tightly regulated proteolysis network, contributing to skin pathophysiology. Evidence from other systems, however, suggests that the relationship between matriptase and prostasin and between the proteases and the inhibitors can be context-dependent. In this study the in vivo zymogen activation and protease inhibition status of matriptase and prostasin were investigated in the human skin. Immunohistochemistry detected high levels of activated prostasin in the granular layer, but only low levels of activated matriptase restricted to the basal layer. Immunoblot analysis of foreskin lysates confirmed this in vivo zymogen activation status and further revealed that HAI-1 but not HAI-2 is the prominent inhibitor for prostasin and matriptase in skin. The zymogen activation status and location of the proteases does not support a close functional relation between matriptase and prostasin in the human skin. The limited role for HAI-2 in the inhibition of matriptase and prostasin is the result of its primarily intracellular localization in basal and spinous layer keratinocytes, which probably prevents the Kunitz inhibitor from interacting with active prostasin or matriptase. In contrast, the cell surface expression of HAI-1 in all viable epidermal layers renders it an effective regulator for matriptase and prostasin. Collectively, our study suggests the importance of tissue distribution and subcellular localization in the functional relationship between proteases and protease inhibitors. Public Library of Science 2018-02-13 /pmc/articles/PMC5811018/ /pubmed/29438412 http://dx.doi.org/10.1371/journal.pone.0192632 Text en © 2018 Lee et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Shiao-Pieng
Kao, Chen-Yu
Chang, Shun-Cheng
Chiu, Yi-Lin
Chen, Yen-Ju
Chen, Ming-Hsing G.
Chang, Chun-Chia
Lin, Yu-Wen
Chiang, Chien-Ping
Wang, Jehng-Kang
Lin, Chen-Yong
Johnson, Michael D.
Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin
title Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin
title_full Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin
title_fullStr Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin
title_full_unstemmed Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin
title_short Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin
title_sort tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, hai-1, and hai-2 in human skin
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811018/
https://www.ncbi.nlm.nih.gov/pubmed/29438412
http://dx.doi.org/10.1371/journal.pone.0192632
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