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

Shiao Pieng Lee, Chen Yu Kao, Shun Cheng Chang, Yi Lin Chiu, Yen Ju Chen, Ming Hsing G. Chen, Chun Chia Chang, Yu Wen Lin, Chien Ping Chiang, Jehng Kang Wang, Chen Yong Lin, Michael D. Johnson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0192632
JournalPLoS One
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 1 2018

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tissue distribution
Tissue Distribution
skin (animal)
Skin
zymogens
Tissue
proteinases
Enzyme Precursors
proteinase inhibitors
Protease Inhibitors
Chemical activation
keratinocytes
serine proteinases
in vivo studies
pathophysiology
proteolysis
immunohistochemistry
Peptide Hydrolases
Proteolysis
Foreskin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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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. / 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.

In: PLoS One, Vol. 13, No. 2, e0192632, 01.02.2018.

Research output: Contribution to journalArticle

Lee, SP, Kao, CY, Chang, SC, Chiu, YL, Chen, YJ, Chen, MHG, Chang, CC, Lin, YW, Chiang, CP, Wang, JK, Lin, CY & Johnson, MD 2018, 'Tissue distribution and subcellular localizations determine in vivo functional relationship among prostasin, matriptase, HAI-1, and HAI-2 in human skin', PLoS One, vol. 13, no. 2, e0192632. https://doi.org/10.1371/journal.pone.0192632
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. In: PLoS One. 2018 ; Vol. 13, No. 2.
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AU - Chen, Ming Hsing G.

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