Epithelial integrity is maintained by a matriptase-dependent proteolytic pathway.
A pericellular proteolytic pathway initiated by the transmembrane serine protease matriptase plays a critical role in the terminal differentiation of epidermal tissues. Matriptase is constitutively expressed in multiple other epithelia, suggesting a putative role of this membrane serine protease in general epithelial homeostasis. Here we generated mice with conditional deletion of the St14 gene, encoding matriptase, and show that matriptase indeed is essential for the maintenance of multiple types of epithelia in the mouse. Thus, embryonic or postnatal ablation of St14 in epithelial tissues of diverse origin and function caused severe organ dysfunction, which was often associated with increased permeability, loss of tight junction function, mislocation of tight junction-associated proteins, and generalized epithelial demise. The study reveals that the homeostasis of multiple simple and stratified epithelia is matriptase-dependent, and provides an important animal model for the exploration of this membrane serine protease in a range of physiological and pathological processes.
List
Karin
K
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Kosa
Peter
P
Szabo
Roman
R
Bey
Alexandra L
AL
Wang
Chao Becky
CB
Molinolo
Alfredo
A
Bugge
Thomas H
TH
D000375:Aging / Q000187:drug effects / Q000473:pathology; D000483:Alleles; D000818:Animals; D004622:Embryo, Mammalian / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000201:enzymology*; D017353:Gene Deletion; D006706:Homeostasis / Q000187:drug effects; D007422:Intestines / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008531:Megacolon / Q000201:enzymology / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009928:Organ Specificity / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012469:Salivary Glands / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D012697:Serine Endopeptidases / Q000172:deficiency / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism
D008565:Membrane Proteins; D013629:Tamoxifen; D012697:Serine Endopeptidases; C485595:matriptase