Matriptase zymogen supports epithelial development, homeostasis and regeneration.Report as inadecuate




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* Corresponding author 1 Department of Veterinary Disease Biology Copenhagen, Denmark 2 Oral and Pharyngeal Cancer Branch - Proteases and Tissue Remodeling Section Bethesda, USA 3 Georgetown University School of Medicine Washington, DC USA 4 USPC - Université Sorbonne Paris Cité 5 PARCC - Paris-Centre de Recherche Cardiovasculaire 6 Department of Cell and Molecular Biology Sao Paulo, Brazil

Abstract : 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.

Abstract : 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.

Abstract : The study demonstrates that the matriptase zymogen is biologically active and is capable of executing developmental and homeostatic functions of the protease.

Keywords : Epithelial cell signaling Zymogen activity Cell surface proteolysis Development





Author: Stine Friis - Daniel Tadeo - Sylvain Le-Gall - Henrik Jessen Jürgensen - Katiuchia Uzzun Sales - Eric Camerer - Thomas Bugge -

Source: https://hal.archives-ouvertes.fr/



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