title: Stem cells migration during skeletal muscle regeneration - the role of Sdf-1/Cxcr4 and Sdf-1/Cxcr7 axis.
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.
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kowalski
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Kołodziejczyk
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Maria
authors.initials: M
authors.lastname: Sikorska
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Jagoda
authors.initials: J
authors.lastname: Płaczkiewicz
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Paulina
authors.initials: P
authors.lastname: Cichosz
authors.affiliation: b Department of Molecular and Translational Oncology , Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology , Warsaw , Poland.|c Department of Immunology, Biochemistry and Nutrition , Medical University of Warsaw , Warsaw , Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Kowalewska
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Władysława
authors.initials: W
authors.lastname: Stremińska
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Jańczyk-Ilach
authors.affiliation: d Laboratory of Systems Biology, Faculty of Biology, University of Warsaw , Warsaw , Poland.|e Laboratory of Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences , Warsaw , Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Koblowska
authors.affiliation: e Laboratory of Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences , Warsaw , Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Fogtman
authors.affiliation: d Laboratory of Systems Biology, Faculty of Biology, University of Warsaw , Warsaw , Poland.|e Laboratory of Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences , Warsaw , Poland.
authors.forename: Roksana
authors.initials: R
authors.lastname: Iwanicka-Nowicka
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Ciemerych
authors.affiliation: a Department of Cytology , Faculty of Biology, University of Warsaw , Warsaw , Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Brzoska
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000473:pathology / Q000502:physiology*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; C514936:CXCR4 protein, mouse; D054377:Chemokine CXCL12; C501897:Cmkor1 protein, mouse; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein
keywords: embryonic stem cells; mesenchymal stem cells; migration; mobilization; muscle regeneration; myoblasts