1. Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis
- Author
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Wladyslawa Streminska, Anna Fogtman, Paulina Cichosz, Kamil Kowalski, Magdalena Kowalewska, Katarzyna Jańczyk-Ilach, Maria A. Ciemerych, Maria Sikorska, Edyta Brzoska, Roksana Iwanicka-Nowicka, Marta Koblowska, Aleksandra Kolodziejczyk, and Jagoda Płaczkiewicz
- Subjects
Male ,rac1 GTP-Binding Protein ,0301 basic medicine ,Receptors, CXCR4 ,Transcription, Genetic ,Biology ,migration ,Myoblasts ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Cell Movement ,medicine ,Animals ,Regeneration ,Myocyte ,Muscle, Skeletal ,cdc42 GTP-Binding Protein ,mobilization ,Cells, Cultured ,Embryonic Stem Cells ,Cell Proliferation ,Stem cell transplantation for articular cartilage repair ,Receptors, CXCR ,Mice, Inbred BALB C ,mesenchymal stem cells ,muscle regeneration ,Myogenesis ,Mesenchymal stem cell ,Skeletal muscle ,Cell Biology ,Embryonic stem cell ,Actins ,Chemokine CXCL12 ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Focal Adhesion Protein-Tyrosine Kinases ,Stem cell ,ITGA7 ,030217 neurology & neurosurgery ,Signal Transduction ,Research Paper - Abstract
The skeletal muscle regeneration occurs due to the presence of tissue specific stem cells - satellite cells. These cells, localized between sarcolemma and basal lamina, are bound to muscle fibers and remain quiescent until their activation upon muscle injury. Due to pathological conditions, such as extensive injury or dystrophy, skeletal muscle regeneration is diminished. Among the therapies aiming to ameliorate skeletal muscle diseases are transplantations of the stem cells. In our previous studies we showed that Sdf-1 (stromal derived factor −1) increased migration of stem cells and their fusion with myoblasts in vitro. Importantly, we identified that Sdf-1 caused an increase in the expression of tetraspanin CD9 - adhesion protein involved in myoblasts fusion. In the current study we aimed to uncover the details of molecular mechanism of Sdf-1 action. We focused at the Sdf-1 receptors - Cxcr4 and Cxcr7, as well as signaling pathways induced by these molecules in primary myoblasts, as well as various stem cells - mesenchymal stem cells and embryonic stem cells, i.e. the cells of different migration and myogenic potential. We showed that Sdf-1 altered actin organization via FAK (focal adhesion kinase), Cdc42 (cell division control protein 42), and Rac-1 (Ras-Related C3 Botulinum Toxin Substrate 1). Moreover, we showed that Sdf-1 modified the transcription profile of genes encoding factors engaged in cells adhesion and migration. As the result, cells such as primary myoblasts or embryonic stem cells, became characterized by more effective migration when transplanted into regenerating muscle.
- Published
- 2016
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