| Homeostatic and Tissue Reparation Defaults in Mice Carrying, Selective, Genetic Invalidation of CXCL12/Proteoglycan Interactions. | |
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MedLine Citation:
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PMID: 23035208 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Interaction with heparan sulfate (HS) proteoglycans is supposed to provide chemokines with the capacity to immobilize on cell surface and extracellular matrix for accomplishing both tissue homing and signalling of attracted cells. However, the consequences of the exclusive invalidation of such interaction on the roles played by endogenous chemokines in vivo, remains unascertained. METHODS AND RESULTS: We engineered a mouse carrying a Cxcl12 gene (Cxcl12(Gagtm)) mutations that preclude interactions with HS structures while they do not affect CXCR4-dependent cell-signalling 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+ haematopoietic precursor cells. Following induced acute ischemia, a marked impaired capacity to support revascularization was observed in Cxcl12(Gagtm/Gagtm) animals associated to a reduced number of infiltrating cells in the ischemic tissue despite the massive expression of CXCL12 isoforms. Importantly, exogenous administration of CXCL12γ, which binds HS with the highest affinity ever reported for a cytokine, fully restores vascular growth, while HS-binding CXCL12γ mutants failed to promote revascularization in Cxcl12(Gagtm/Gagtm) animals. CONCLUSIONS: These findings prove the role played by HS-interactions in the functions of CXCL12 both in homeostasis and physiopathological settings and document originally the paradigm of chemokine-immobilisation in vivo. |
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Authors:
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Patricia Rueda; Adèle Richart; Alice Récalde; Pamela Gasse; José Vilar; Coralie Guérin; Hugues Lortat-Jacob; Paulo Vieira; Françoise Baleux; Fabrice Chretien; Fernando Arenzana-Seisdedos; Jean-Sébastien Silvestre |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-10-3 |
Journal Detail:
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Title: Circulation Volume: - ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1 INSERM U819, Paris, France; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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