Matriptase zymogen supports epithelial development, homeostasis and regeneration View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-12

AUTHORS

Stine Friis, Daniel Tadeo, Sylvain M. Le-Gall, Henrik Jessen Jürgensen, Katiuchia Uzzun Sales, Eric Camerer, Thomas H. Bugge

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. More... »

PAGES

46

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s12915-017-0384-4

    DOI

    http://dx.doi.org/10.1186/s12915-017-0384-4

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1085705099

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28571576


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