Matriptase activation connects tissue factor–dependent coagulation initiation to epithelial proteolysis and signaling

Autor: Thomas H. Bugge, Melody Lee, Roman Szabo, Sylvain M. Le Gall, Daniel Kirchhofer, Eric Camerer, Charles S. Craik
Přispěvatelé: Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institutes of Health [Bethesda] (NIH), University of California [San Francisco] (UCSF), University of California, Genentech, Inc., Genentech, Inc. [San Francisco], Camerer, Eric, MECANISMES INTEGRES DE L'INFLAMMATION - La règlulation de l'intégrité vasculaire par les GPCRs - - GROVI2010 - ANR-10-MIDI-0003 - MI2 - VALID, Signalisation PAR2 et cibles thérapeutiques associées dans les pathologies cutanées inflammatoires. - - PAR-2-PATH2015 - ANR-15-CE14-0009 - AAPG2015 - VALID, University of California [San Francisco] (UC San Francisco), University of California (UC), The Ile-de-France Region (E.C.), INSERM Avenir (E.C.), ANR-10-MIDI-0003,GROVI,La règlulation de l'intégrité vasculaire par les GPCRs(2010), ANR-15-CE14-0009,PAR-2-PATH,Signalisation PAR2 et cibles thérapeutiques associées dans les pathologies cutanées inflammatoires.(2015)
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
[SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology
[SDV]Life Sciences [q-bio]
[SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Biochemistry
Transactivation
0302 clinical medicine
Inside BLOOD Commentary
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Thromboplastin
[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology
biology
medicine.diagnostic_test
Serine Endopeptidases
Proteolytic enzymes
[SDV.BBM.MN]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular Networks [q-bio.MN]
[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology
Hematology
Cell biology
[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
[SDV] Life Sciences [q-bio]
030220 oncology & carcinogenesis
Factor Xa
MCF-7 Cells
Signal transduction
Signal Transduction
Proteases
Proteolysis
Immunology
Factor VIIa
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
03 medical and health sciences
Tissue factor
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Cell Line
Tumor
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Humans
Receptor
PAR-2
Matriptase
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Blood Coagulation
Epithelial Cells
Cell Biology
Enzyme Activation
030104 developmental biology
[SDV.BBM.MN] Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular Networks [q-bio.MN]
biology.protein
Mutant Proteins
[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
HeLa Cells
Zdroj: Blood
Blood, American Society of Hematology, 2016, 127 (25), pp.3260-3269. ⟨10.1182/blood-2015-11-683110⟩
Blood, 2016, 127 (25), pp.3260-3269. ⟨10.1182/blood-2015-11-683110⟩
ISSN: 0006-4971
1528-0020
DOI: 10.1182/blood-2015-11-683110⟩
Popis: The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.
Databáze: OpenAIRE
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