Homeostatic and Tissue Reparation Defaults in Mice Carrying Selective Genetic Invalidation of CXCL12/Proteoglycan Interactions
| Autor: | Fabrice Chrétien, Françoise Baleux, Coralie L. Guerin, Paulo José Cardoso Vieira, Alice Recalde, Jean-Sébastien Silvestre, José Vilar, Patricia Rueda, Hugues Lortat-Jacob, Adèle Richart, Paméla Gasse, Fernando Arenzana-Seisdedos |
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| Přispěvatelé: | Pham, Cécile, Pathogénie Virale, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Institut de biologie structurale (IBS - UMR 5075 ), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Lymphopoïèse, Chimie des biomolécules, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris] (IP), This work was supported by grants from Agence Nationale de la Recherche (ANR, Chemoglycan, NT05-4_41967, Chemrepair 2010-BLAN112702), INSERM, Institut Pasteur PTR-395, Mizutani Fundation (Japan) and by institutional funding from INSERM. J.S.S is a recipient of a Contrat d'Interface from Assistance Publique-Hôpitaux de Paris and supported by 'Fondation pour la Recherche Médicale'. P.R and P.G are recipients of ANR fellowships. A.Récalde is a recipient of fellowships from Fondation pour la Recherche Médicale and from Région Ile de France., Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ) |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Chemokine
Cell signaling Transcription Genetic Cell Neovascularization Physiologic Article Extracellular matrix 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology Ischemia Physiology (medical) Precursor cell medicine Animals Homeostasis Protein Isoforms RNA Messenger Muscle Skeletal [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology 030304 developmental biology 0303 health sciences biology Heparin Heparan sulfate Chemokine CXCL12 biological factors Cell biology Hindlimb medicine.anatomical_structure [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Proteoglycan chemistry Biochemistry 030220 oncology & carcinogenesis Models Animal embryonic structures biology.protein Proteoglycans biological phenomena cell phenomena and immunity Cardiology and Cardiovascular Medicine Homing (hematopoietic) |
| Zdroj: | Circulation Circulation, 2012, 126 (15), pp.1882-95. ⟨10.1161/CIRCULATIONAHA.112.113290⟩ Circulation, American Heart Association, 2012, 126 (15), pp.1882-95. ⟨10.1161/CIRCULATIONAHA.112.113290⟩ Circulation, American Heart Association, 2012, 126 (15), pp.1882-95. 〈10.1161/CIRCULATIONAHA.112.113290〉 |
| ISSN: | 0009-7322 1524-4539 |
| DOI: | 10.1161/CIRCULATIONAHA.112.113290⟩ |
| Popis: | Background— Interaction with heparan sulfate proteoglycans is supposed to provide chemokines with the capacity to immobilize on cell surface and extracellular matrix for accomplishing both tissue homing and signaling of attracted cells. However, the consequences of the exclusive invalidation of such interaction on the roles played by endogenous chemokines in vivo remain unascertained. Methods and Results— We engineered a mouse carrying a Cxcl12 gene ( Cxcl12 Gagtm ) mutation that precludes interactions with heparan sulfate structures while not affecting CXCR4-dependent cell signaling of CXCL12 isoforms (α, β, γ). Cxcl12 Gagtm/Gagtm mice develop normally, express normal levels of total and isoform-specific Cxcl12 mRNA, and show increased counting of circulating CD34 + hematopoietic precursor cells. After induced acute ischemia, a marked impaired capacity to support revascularization was observed in Cxcl12 Gagtm/Gagtm animals associated with a reduced number of infiltrating cells in the ischemic tissue despite the massive expression of CXCL12 isoforms. Importantly, exogenous administration of CXCL12γ, which binds heparan sulfate with the highest affinity ever reported for a cytokine, fully restores vascular growth, whereas heparan sulfate–binding CXCL12γ mutants failed to promote revascularization in Cxcl12 Gagtm/Gagtm animals. Conclusion— These findings prove the role played by heparan sulfate interactions in the functions of CXCL12 in both homeostasis and physiopathological settings and document for the first time the paradigm of chemokine immobilization in vivo. |
| Databáze: | OpenAIRE |
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