Matriptase inhibition by hepatocyte growth factor activator inhibitor-1 is essential for placental development View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2007-03

AUTHORS

R Szabo, A Molinolo, K List, T H Bugge

ABSTRACT

Hepatocyte growth factor activator inhibitor-1 (HAI-1) is a Kunitz-type transmembrane serine protease inhibitor that forms inhibitor complexes with several trypsin-like serine proteases and is required for mouse placental development and embryo survival. Here we show that the essential function of HAI-1 in placentation and all other embryonic processes is to restrict the activity of the type II transmembrane serine protease, matriptase. Enzymatic gene trapping of matriptase combined with HAI-1 immunohistochemistry revealed that matriptase is co-expressed with HAI-1 in both extraembryonic and embryonic tissues. As early as embryonic day 8.5, matriptase and HAI-1 were expressed in a population of chorionic trophoblasts. Ablation of HAI-1 disrupted the epithelial integrity of this cell population, causing disorganized laminin deposition and altered expression of E-cadherin and beta-catenin. This led to a complete loss of undifferentiated chorionic trophoblasts after embryonic day 9.5 and prevented the formation of the placental labyrinth. Genetic ablation of matriptase activity in HAI-1-deficient embryos, however, restored the integrity of chorionic trophoblasts and enabled placental labyrinth formation and development to term. Furthermore, matriptase/HAI-1 double-deficient mice were phenotypically indistinguishable from matriptase single-deficient littermates. More... »

PAGES

1209966

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1209966

DOI

http://dx.doi.org/10.1038/sj.onc.1209966

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022804100

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16983341


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