Matriptase and prostasin proteolytic activities are differentially regulated in normal and wounded skin
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RESEARCH ARTICLE
Matriptase and prostasin proteolytic activities are differentially regulated in normal and wounded skin Shun‑Cheng Chang1,2 · Chien‑Ping Chiang3,4 · Chih‑Hsin Lai5 · Po‑Wen A. Du6 · Yu‑Sin Hung4 · Yu‑Hsuan Chen4 · Hui‑Yu Yang4 · Hao‑Yu Fang4 · Shiao‑Pieng Lee7,8 · Hung‑Jen Tang9 · Jehng‑Kang Wang4 · Michael D. Johnson6 · Chen‑Yong Lin6 Received: 21 February 2020 / Accepted: 2 June 2020 © Japan Human Cell Society 2020
Abstract Orchestrated control of multiple overlapping and sequential processes is required for the maintenance of epidermal homeostasis and the response to and recovery from a variety of skin insults. Previous studies indicate that membrane-associated serine protease matriptase and prostasin play essential roles in epidermal development, differentiation, and barrier formation. The control of proteolysis is a highly regulated process, which depends not only on gene expression but also on zymogen activation and the balance between protease and protease inhibitor. Subcellular localization can affect the accessibility of protease inhibitors to proteases and, thus, also represents an integral component of the control of proteolysis. To understand how membrane-associated proteolysis is regulated in human skin, these key aspects of matriptase and prostasin were determined in normal and injured human skin by immunohistochemistry. This staining shows that matriptase is expressed predominantly in the zymogen form at the periphery of basal and spinous keratinocytes, and prostasin appears to be constitutively activated at high levels in polarized organelle-like structures of the granular keratinocytes in the adjacent quiescent skin. The membrane-associated proteolysis appears to be elevated via an increase in matriptase zymogen activation and prostasin protein expression in areas of skin recovering from epidermal insults. There was no noticeable change observed in other regulatory aspects, including the expression and tissue distribution of their cognate inhibitors HAI-1 and HAI-2. This study reveals that the membrane-associated proteolysis may be a critical epidermal mechanism involved in responding to, and recovering from, damage to human skin. Keywords Matriptase · Prostasin · HAI-1 · HAI-2 · Skin
* Hung‑Jen Tang [email protected]
5
Department of Dentistry Renai Branch, Taipei City Hospital, Taipei 106, Taiwan
* Jehng‑Kang Wang [email protected]
6
Lombardi Comprehensive Cancer Center, Department of Oncology, Georgetown University, W412 Research Building, 3970 Reservoir Road NW, Washington, DC 20057, USA
* Chen‑Yong Lin [email protected]
7
Division of Plastic Surgery, Integrated Burn and Wound Care Center, Department of Surgery, Shuang-Ho Hospital, New Taipei City 235, Taiwan
Department of Biomedical Engineering, National Defense Medical Center, Taipei 114, Taiwan
8
2
Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
Department of Oral and Maxillofacial Surgery, Tri-Service General Hospital, Taipei 1
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