Lysyl oxidase-like protein-2 regulates sprouting angiogenesis and type IV collagen assembly in the endothelial basement membrane
| Autor: | Cathy Pichol-Thievend, Stéphane Germain, Florence Ruggiero, Nicholas Brechot, Michel Caron, Laurent Muller, Emilie Guillon, Julie Hardouin, Marine Bignon, Eric Etienne, A. Barret, Luiz Nasciutti, Marilyne Malbouyres, Jérémie Teillon, Raymonde Joubert-Caron, Catherine Monnot |
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| Přispěvatelé: | Angiogénèse embryonnaire et pathologique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre interdisciplinaire de recherche en biologie (CIRB), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2011 |
| Předmět: |
Collagen Type IV
Angiogenesis Immunology Neovascularization Physiologic Lysyl oxidase Biology Biochemistry Basement Membrane Cell Line Extracellular matrix Mice 03 medical and health sciences Type IV collagen 0302 clinical medicine [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Cell Movement medicine Animals Humans Zebrafish 030304 developmental biology Basement membrane Sprouting angiogenesis 0303 health sciences LOXL2 Endothelial Cells Cell Biology Hematology Zebrafish Proteins Molecular biology Cell Hypoxia Extracellular Matrix Up-Regulation Cell biology Mice Inbred C57BL medicine.anatomical_structure 030220 oncology & carcinogenesis Basal lamina Amino Acid Oxidoreductases Endothelium Vascular |
| Zdroj: | Blood Blood, American Society of Hematology, 2011, 118 (14), pp.3979--3989. ⟨10.1182/blood-2010-10-313296⟩ Blood, 2011, 118 (14), pp.3979--3989. ⟨10.1182/blood-2010-10-313296⟩ |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2010-10-313296 |
| Popis: | Sprouting angiogenesis is associated with extensive extracellular matrix (ECM) remodeling. The molecular mechanisms involved in building the vascular microenvironment and its impact on capillary formation remain elusive. We therefore performed a proteomic analysis of ECM from endothelial cells maintained in hypoxia, a major stimulator of angiogenesis. Here, we report the characterization of lysyl oxidase-like protein-2 (LOXL2) as a hypoxia-target expressed in neovessels and accumulated in the endothelial ECM. LOXL2 belongs to the lysyl oxidase family of secreted enzymes involved in ECM crosslinking. Knockdown experiments in Tg(fli1:egfp)y1 zebrafish embryos resulted in lack of intersegmental vessel circulation and demonstrated LOXL2 involvement in proper capillary formation. Further investigation in vitro by loss and gain of function experiments confirmed that LOXL2 was required for tubulogenesis in 3D fibrin gels and demonstrated that this enzyme was required for collagen IV assembly in the ECM. In addition, LOXL2 depletion down-regulated cell migration and proliferation. These data suggest a major role for LOXL2 in the organization of endothelial basal lamina and in the downstream mechanotransductive signaling. Altogether, our study provides the first evidence for the role of LOXL2 in regulating angiogenesis through collagen IV scaffolding. |
| Databáze: | OpenAIRE |
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