Defective angiogenesis in CXCL12 mutant mice impairs skeletal muscle regeneration
| Autor: | David Briand, Aurore Besnard, Fabrice Chrétien, Mylène Fefeu, David Hardy, Paméla Gasse, Pierre Rocheteau, Fernando Arenzana-Seisdedos |
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| Přispěvatelé: | Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), Pathogénie Virale Moléculaire, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was financially supported by AFM-vaincre les myopathies, Fondation'Les Gueules Cassées,'Institut Pasteur, and Région Ile de France., Hardy, David, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Chemokine lcsh:Diseases of the musculoskeletal system Angiogenesis MESH: Mice Mutant Strains Endothelial cells Skeletal muscle [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] Mice 0302 clinical medicine Fibrosis [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] Vasculogenesis Freezing Orthopedics and Sports Medicine MESH: Animals MESH: Endothelial Cells Receptor [SDV.BDD]Life Sciences [q-bio]/Development Biology MESH: Muscle Skeletal biology Chemistry MESH: Regeneration MESH: Satellite Cells Skeletal Muscle CXCL12 Cell biology medicine.anatomical_structure embryonic structures Stem cell MESH: Chemokine CXCL12 biological phenomena cell phenomena and immunity MESH: Neovascularization Physiologic Satellite Cells Skeletal Muscle MESH: Mice Transgenic Heparan sulfates Neovascularization Physiologic Mice Transgenic [SDV.BC]Life Sciences [q-bio]/Cellular Biology 03 medical and health sciences MESH: Gene Expression Profiling MESH: Mice Inbred C57BL [SDV.BDD] Life Sciences [q-bio]/Development Biology Muscle stem cells Extracellular medicine Regeneration Animals Muscle Skeletal Molecular Biology MESH: Mice [SDV.BC] Life Sciences [q-bio]/Cellular Biology MESH: Elapid Venoms Elapid Venoms Research Gene Expression Profiling Cell Biology medicine.disease MESH: Male biological factors Chemokine CXCL12 Mice Mutant Strains Mice Inbred C57BL 030104 developmental biology biology.protein MESH: Heparan Sulfate Proteoglycans lcsh:RC925-935 030217 neurology & neurosurgery Heparan Sulfate Proteoglycans MESH: Freezing |
| Zdroj: | Skeletal Muscle Skeletal Muscle, 2019, 9 (1), pp.25. ⟨10.1186/s13395-019-0210-5⟩ Skeletal Muscle, Vol 9, Iss 1, Pp 1-15 (2019) Skeletal Muscle, BioMed Central, 2019, 9 (1), pp.25. ⟨10.1186/s13395-019-0210-5⟩ |
| ISSN: | 2044-5040 |
| Popis: | BackgroundDuring muscle regeneration, the chemokine CXCL12 (SDF-1) and the synthesis of some specific heparan sulfates (HS) have been shown to be critical. CXCL12 activity has been shown to be heavily influenced by its binding to extracellular glycosaminoglycans (GAG) by modulating its presentation to its receptors and by generating haptotactic gradients. Although CXCL12 has been implicated in several phases of tissue repair, the influence of GAG binding under HS influencing conditions such as acute tissue destruction remains understudied.MethodsTo investigate the role of the CXCL12/HS proteoglycan interactions in the pathophysiology of muscle regeneration, we performed two models of muscle injuries (notexin and freeze injury) in mutant CXCL12Gagtm/Gagtmmice, where the CXCL12 gene having been selectively mutated in critical binding sites of CXCL12 to interact with HS. Histological, cytometric, functional transcriptomic, and ultrastructure analysis focusing on the satellite cell behavior and the vessels were conducted on muscles before and after injuries. Unless specified, statistical analysis was performed with the Mann-Whitney test.ResultsWe showed that despite normal histology of the resting muscle and normal muscle stem cell behavior in the mutant mice, endothelial cells displayed an increase in the angiogenic response in resting muscle despite the downregulated transcriptomic changes induced by the CXCL12 mutation. The regenerative capacity of the CXCL12-mutated mice was only delayed after a notexin injury, but a severe damage by freeze injury revealed a persistent defect in the muscle regeneration of CXCL12 mutant mice associated with vascular defect and fibroadipose deposition with persistent immune cell infiltration.ConclusionThe present study shows that CXCL12 is crucial for proper muscle regeneration. We highlight that this homing molecule could play an important role in drastic muscle injuries and that the regeneration defect could be due to an impairment of angiogenesis, associated with a long-lasting fibro-adipogenic scar. |
| Databáze: | OpenAIRE |
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