Journal
BMC BIOLOGY
Volume 15, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s12915-017-0384-4
Keywords
Development; Cell surface proteolysis; Epithelial cell signaling; Zymogen activity
Categories
Funding
- NIDCR Intramural Research Program
- Harboe Foundation
- Lundbeck Foundation
- Foundation of 17.12.1981.
- French National Research Agency [ANR-15-CE14-0009]
- Sao Paolo Research Foundation (FAPESP)
- Agence Nationale de la Recherche (ANR) [ANR-15-CE14-0009] Funding Source: Agence Nationale de la Recherche (ANR)
- Lundbeck Foundation [R140-2013-13193] Funding Source: researchfish
- The Danish Cancer Society [R90-A5989] Funding Source: researchfish
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Background: Matriptase is a membrane serine protease essential for epithelial development, homeostasis, and regeneration, as well as a central orchestrator of pathogenic pericellular signaling in the context of inflammatory and proliferative diseases. Matriptase is an unusual protease in that its zymogen displays measurable enzymatic activity. Results: Here, we used gain and loss of function genetics to investigate the possible biological functions of zymogen matriptase. Unexpectedly, transgenic mice mis-expressing a zymogen-locked version of matriptase in the epidermis displayed pathologies previously reported for transgenic mice mis-expressing wildtype epidermal matriptase. Equally surprising, mice engineered to express only zymogen-locked endogenous matriptase, unlike matriptase null mice, were viable, developed epithelial barrier function, and regenerated the injured epithelium. Compatible with these observations, wildtype and zymogen-locked matriptase were equipotent activators of PAR-2 inflammatory signaling. Conclusion: The study demonstrates that the matriptase zymogen is biologically active and is capable of executing developmental and homeostatic functions of the protease.
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