دورية أكاديمية
Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition.
| العنوان: | Neutrophil Extracellular Traps Drive Endothelial-to-Mesenchymal Transition. |
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| المؤلفون: | Pieterse E; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Rother N; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Garsen M; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Hofstra JM; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Satchell SC; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Hoffmann M; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Loeven MA; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Knaapen HK; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., van der Heijden OWH; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Berden JHM; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., Hilbrands LB; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.)., van der Vlag J; From the Nephrology Research Laboratory, Department of Nephrology (E.P., N.R., M.G., J.M.H., M.A.L., J.H.M.B., L.B.H., J.v.d.V.), Department of Rheumatology (H.K.K.), and Department of Obstetrics & Gynecology (O.W.H.v.d.H.), Radboud University Medical Center, Nijmegen, The Netherlands; Academic Renal Unit, School of Clinical Science, University of Bristol, United Kingdom (S.C.S.); and Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich Alexander University of Erlangen-Nuremberg, Germany (M.H.). johan.vandervlag@radboudumc.nl. |
| المصدر: | Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2017 Jul; Vol. 37 (7), pp. 1371-1379. Date of Electronic Publication: 2017 May 11. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 9505803 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4636 (Electronic) Linking ISSN: 10795642 NLM ISO Abbreviation: Arterioscler Thromb Vasc Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 1998- : Baltimore, Md. : Lippincott Williams & Wilkins Original Publication: Dallas, TX : American Heart Association, c1995- |
| مواضيع طبية MeSH: | Epithelial-Mesenchymal Transition*, Extracellular Traps/*metabolism , Human Umbilical Vein Endothelial Cells/*metabolism , Kidney Glomerulus/*metabolism , Lupus Nephritis/*metabolism , Neutrophils/*metabolism, Adult ; Animals ; Antigens, CD/metabolism ; Cadherins/metabolism ; Capillary Permeability ; Clathrin/metabolism ; Disease Models, Animal ; Endocytosis ; Extracellular Traps/immunology ; Human Umbilical Vein Endothelial Cells/immunology ; Human Umbilical Vein Endothelial Cells/pathology ; Humans ; Kidney Glomerulus/immunology ; Kidney Glomerulus/pathology ; Leukocyte Elastase/metabolism ; Lupus Nephritis/immunology ; Lupus Nephritis/pathology ; Mice, Inbred CBA ; Mice, Inbred MRL lpr ; Neutrophils/immunology ; Neutrophils/pathology ; Phagocytosis ; Receptor for Advanced Glycation End Products/metabolism ; Severity of Illness Index ; Signal Transduction ; Time Factors ; Young Adult ; beta Catenin/metabolism |
| مستخلص: | Objective: An excessive release and impaired degradation of neutrophil extracellular traps (NETs) leads to the continuous exposure of NETs to the endothelium in a variety of hematologic and autoimmune disorders, including lupus nephritis. This study aims to unravel the mechanisms through which NETs jeopardize vascular integrity. Approach and Results: Microvascular and macrovascular endothelial cells were exposed to NETs, and subsequent effects on endothelial integrity and function were determined in vitro and in vivo. We found that endothelial cells have a limited capacity to internalize NETs via the receptor for advanced glycation endproducts. An overflow of the phagocytic capacity of endothelial cells for NETs resulted in the persistent extracellular presence of NETs, which rapidly altered endothelial cell-cell contacts and induced vascular leakage and transendothelial albumin passage through elastase-mediated proteolysis of the intercellular junction protein VE-cadherin. Furthermore, NET-associated elastase promoted the nuclear translocation of junctional β-catenin and induced endothelial-to-mesenchymal transition in cultured endothelial cells. In vivo, NETs could be identified in kidney samples of diseased MRL/lpr mice and patients with lupus nephritis, in whom the glomerular presence of NETs correlated with the severity of proteinuria and with glomerular endothelial-to-mesenchymal transition. Conclusions: These results indicate that an excess of NETs exceeds the phagocytic capacity of endothelial cells for NETs and promotes vascular leakage and endothelial-to-mesenchymal transition through the degradation of VE-cadherin and the subsequent activation of β-catenin signaling. Our data designate NET-associated elastase as a potential therapeutic target in the prevention of endothelial alterations in diseases characterized by aberrant NET release. (© 2017 American Heart Association, Inc.) |
| فهرسة مساهمة: | Keywords: endothelial cells; extracellular traps; leukocyte elastase; lupus erythematosus, systemic; lupus nephritis |
| المشرفين على المادة: | 0 (AGER protein, human) 0 (Ager protein, mouse) 0 (Antigens, CD) 0 (CTNNB1 protein, human) 0 (CTNNB1 protein, mouse) 0 (Cadherins) 0 (Clathrin) 0 (Receptor for Advanced Glycation End Products) 0 (beta Catenin) 0 (cadherin 5) EC 3.4.21.37 (Leukocyte Elastase) |
| تواريخ الأحداث: | Date Created: 20170513 Date Completed: 20170710 Latest Revision: 20180522 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1161/ATVBAHA.117.309002 |
| PMID: | 28495931 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1524-4636 |
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| DOI: | 10.1161/ATVBAHA.117.309002 |