Increased matriptase zymogen activation in inflammatory skin disorders.

Abstract

Matriptase, a type 2 transmembrane serine protease, and its inhibitor hepatocyte growth factor activator inhibitor (HAI)-1 are required for normal epidermal barrier function, and matriptase activity is tightly regulated during this process. We therefore hypothesized that this protease system might be deregulated in skin disease. To test this, we examined the level and activation state of matriptase in examples of 23 human skin disorders. We first examined matriptase and HAI-1 protein distribution in normal epidermis. Matriptase was detected at high levels at cell-cell junctions in the basal layer and spinous layers but was present at minimal levels in the granular layer. HAI-1 was distributed in a similar pattern, except that high-level expression was retained in the granular layer. This pattern of expression was retained in most skin disorders. We next examined the distribution of activated matriptase. Although activated matriptase is not detected in normal epidermis, a dramatic increase is seen in keratinocytes at the site of inflammation in 16 different skin diseases. To gain further evidence that activation is associated with inflammatory stimuli, we challenged HaCaT cells with acidic pH or H(2)O(2) and observed matriptase activation. These findings suggest that inflammation-associated reactive oxygen species and tissue acidity may enhance matriptase activation in some skin diseases.

• Authors: Cheng-Jueng Chen, Bai-Yao Wu, Pai-In Tsao, Chi-Yung Chen, Mei-Hsuan Wu, Yee Lam E Chan, Herng-Sheng Lee, Michael D Johnson, Richard L Eckert, Ya-Wen Chen, Fengpai Chou, Jehng-Kang Wang, Chen-Yong Lin
• Journal: American journal of physiology. Cell physiology (Am J Physiol Cell Physiol) Vol. 300 Issue 3 Pg. C406-15 (Mar 2011) ISSN: 1522-1563 [Electronic] United States
• PMID: 21123732 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Inflammation Mediators
• Proteinase Inhibitory Proteins, Secretory
• SPINT1 protein, human
• Serine Proteinase Inhibitors
• Serine Endopeptidases
• ST14 protein, human

Topics

• Cell Line, Transformed
• Dermatitis (enzymology, metabolism, pathology)
• Down-Regulation (physiology)
• Enzyme Activation (physiology)
• Epidermis (enzymology, metabolism, pathology)
• Epithelial Cells (enzymology, ultrastructure)
• Humans
• Inflammation Mediators (metabolism, physiology)
• Intercellular Junctions (enzymology, metabolism, ultrastructure)
• Keratinocytes (enzymology, ultrastructure)
• Proteinase Inhibitory Proteins, Secretory (metabolism, physiology)
• Serine Endopeptidases (metabolism)
• Serine Proteinase Inhibitors (metabolism, pharmacology)
• Up-Regulation (physiology)