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Matriptase zymogen supports epithelial development, homeostasis and regeneration
Stine Friis1,2, Daniel Tadeo1,3, Sylvain M Le-Gall4,5
1Proteases and Tissue Remodeling Section, Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Room 320, Bethesda, MD, 20892, USA.
BMC Biology
|June 3, 2017
Summary
The matriptase zymogen, an enzyme precursor, is biologically active and performs essential functions in epithelial development and repair. This finding reveals new roles for this protease in maintaining tissue health.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- Matriptase is a crucial membrane serine protease for epithelial homeostasis and regeneration.
- It plays a role in inflammatory and proliferative diseases.
- Unusually, matriptase zymogen exhibits measurable enzymatic activity.
Purpose of the Study:
- To investigate the biological functions of zymogen matriptase using genetic approaches.
- To determine if the zymogen form of matriptase possesses inherent biological activity.
- To compare the functions of zymogen-locked matriptase with wildtype and null variants.
Main Methods:
- Gain and loss of function genetics in mouse models.
- Generation of transgenic mice expressing zymogen-locked matriptase.
- Analysis of epithelial barrier function and regeneration capacity.
- Assessment of protease-activated receptor-2 (PAR-2) signaling.
Main Results:
- Mice expressing a zymogen-locked matriptase in the epidermis showed pathologies similar to wildtype matriptase mis-expression.
- Mice expressing only zymogen-locked endogenous matriptase were viable and developed normal epithelial barrier function.
- Zymogen-locked matriptase was as effective as wildtype matriptase in activating PAR-2 signaling.
- Zymogen-locked matriptase facilitated epithelial regeneration after injury.
Conclusions:
- The matriptase zymogen is biologically active.
- The zymogen form of matriptase can execute developmental and homeostatic functions.
- Matriptase zymogen plays a significant role in epithelial biology and repair mechanisms.
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