Matriptase zymogen supports epithelial development, homeostasis and regeneration.
BMC Biol
; 15(1): 46, 2017 06 01.
Article
em En
| MEDLINE
| ID: mdl-28571576
ABSTRACT
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regeneração
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Serina Endopeptidases
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Precursores Enzimáticos
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Epitélio
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Homeostase
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article