Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis.
Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation. Hemizygous and homozygous Magic-F1 transgenic mice displayed constitutive muscle hypertrophy.



Here we describe microarray analysis on Magic-F1 myogenic progenitor cells showing an altered gene signatures on muscular hypertrophy and angiogenesis compared to wild-type cells. In addition, we performed a functional analysis on Magic-F1+/+ transgenic mice versus controls using treadmill test.



We demonstrated that Magic-F1+/+ mice display an increase in muscle mass and cross-sectional area leading to an improvement in running performance. Moreover, the presence of MAGIC-F1 affected positively the vascular network, increasing the vessel number in fast twitch fibers. Finally, the gene expression profile analysis of Magic-F1+/+ satellite cells evidenced transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation.



We showed that MAGIC-F1-induced muscle hypertrophy affects positively vascular network, increasing vessel number in fast twitch fibers. This was due to unique features of mammalian skeletal muscle and its remarkable ability to adapt promptly to different physiological demands by modulating the gene expression profile in myogenic progenitors.
Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland
Flavio
F
Ronzoni
Department of Public Health, Experimental Medicine and Forensic, Faculty of Medicine, University of Pavia, Pavia, Italy|Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy
Gabriele
G
Ceccarelli
Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, Belgium
Ilaria
I
Perini
Department of Public Health, Experimental Medicine and Forensic, Faculty of Medicine, University of Pavia, Pavia, Italy|Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy
Laura
L
Benedetti
Department of Biomedical, Biotechnological and Translational Sciences (S.Bi.Bi.T.), Anatomy and Histology Unit, University of Parma, Parma, Italy
Daniela
D
Galli
Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy|Department of Industrial and Information, University of Pavia, Pavia, Italy
Francesca
F
Mulas
Department of Public Health, Experimental Medicine and Forensic, Faculty of Medicine, University of Pavia, Pavia, Italy|Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy
Martina
M
Balli
Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy|Department of Industrial and Information, University of Pavia, Pavia, Italy
Giovanni
G
Magenes
Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy|Department of Industrial and Information, University of Pavia, Pavia, Italy
Riccardo
R
Bellazzi
Department of Public Health, Experimental Medicine and Forensic, Faculty of Medicine, University of Pavia, Pavia, Italy|Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy
Gabriella C
GC
De Angelis
Department of Public Health, Experimental Medicine and Forensic, Faculty of Medicine, University of Pavia, Pavia, Italy|Center of Health Technologies (C.H.T), University of Pavia, Pavia, Italy|Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department of Development and Regeneration, KU Leuven, Belgium
Maurilio
M
Sampaolesi
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005080:Exercise Test; D005260:Female; D015870:Gene Expression; D006801:Humans; D006984:Hypertrophy; D051379:Mice; D008822:Mice, Transgenic; D024510:Muscle Development / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000254:growth & development / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met / Q000819:agonists*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000378:metabolism*
D011994:Recombinant Proteins; C533045:magic-factor 1 protein, mouse; D019859:Proto-Oncogene Proteins c-met
Myogenic progenitor cells; angiogenesis; microarray
analysis; muscle hypertrophy; recombinant proteins; transgenic mice