Matriptase Initiates Activation of Epidermal Pro-kallikrein and Disease Onset in a Mouse Model of Netherton Syndrome

Overview

Journal Nat Genet

Specialty Genetics

Date 2010 Jul 27

PMID 20657595

Citations 43

Authors

Katiuchia Uzzun Sales

Andrius Masedunskas

Alexandra L Bey

Amber L Rasmussen

Roberto Weigert

Karin List

Roman Szabo

Paul A Overbeek

Thomas H Bugge

Affiliations

Soon will be listed here.

Abstract

Deficiency in the serine protease inhibitor LEKTI is the etiological origin of Netherton syndrome, which causes detachment of the stratum corneum and chronic inflammation. Here we show that the membrane protease matriptase initiates Netherton syndrome in a LEKTI-deficient mouse model by premature activation of a pro-kallikrein cascade. Auto-activation of pro-inflammatory pro-kallikrein-related peptidases that are associated with stratum corneum detachment was either low or undetectable, but they were efficiently activated by matriptase. Ablation of matriptase from LEKTI-deficient mice dampened inflammation, eliminated aberrant protease activity, prevented detachment of the stratum corneum, and improved the barrier function of the epidermis. These results uncover a pathogenic matriptase-pro-kallikrein pathway that could operate in several human skin and inflammatory diseases.

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