Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis

Title:Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis

Volume: 18 Issue: 4

Author(s): Flavio Ronzoni, Gabriele Ceccarelli, Ilaria Perini, Laura Benedetti, Daniela Galli, Francesca Mulas, Martina Balli, Giovanni Magenes, Riccardo Bellazzi, Gabriella C. De Angelis and Maurilio Sampaolesi*

Affiliation:

• Translational Cardiomyology Laboratory, Stem Cell Biology and Embryology Unit, Department Development and Regeneration, KU Leuven,Belgium

Keywords: Myogenic progenitor cells, recombinant proteins, muscle hypertrophy, angiogenesis, transgenic mice, microarray analysis.

Abstract: Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Cite this article as:

Ronzoni Flavio, Ceccarelli Gabriele, Perini Ilaria, Benedetti Laura, Galli Daniela, Mulas Francesca, Balli Martina, Magenes Giovanni, Bellazzi Riccardo, De Angelis C. Gabriella and Sampaolesi Maurilio*, Met-Activating Genetically Improved Chimeric Factor-1 Promotes Angiogenesis and Hypertrophy in Adult Myogenesis, Current Pharmaceutical Biotechnology 2017; 18 (4) . https://dx.doi.org/10.2174/1389201018666170201124602

DOI https://dx.doi.org/10.2174/1389201018666170201124602	Print ISSN 1389-2010
Publisher Name Bentham Science Publisher	Online ISSN 1873-4316