Benedetti, Laura

Conte, Silvio

Cusella De Angelis, Gabriella

Galli, Daniela

Grifone, Stefano

Micheletti, Rudi

Ronzoni, Flavio

Sampaolesi, Maurilio

Firenze University Press: E-Journals

IJAE Vol. 115, n. 1/2 (Supplement), 2010
151
Gene signature of muscle hypertrophy
Flavio Ronzoni1, Silvio Conte1, Daniela Galli1, Rudi Micheletti1, Stefano Grifone1, Laura Benedetti1, 
Gabriella Cusella De Angelis1, Maurilio Sampaolesi1,2
1 Department of Experimental Medicine, Human Anatomy Unit, University of Pavia, Italy
2 Translational Cardiomyology Laboratory, SCIL K.U. Leuven, Belgium
Hepatocyte Growth Factor (HGF) is a pleiotropic cytokine of mesenchymal origin 
that mediates cell proliferation, survival, motility and morphogenesis. Its high affinity 
receptor, the tyrosine kinase Met, is expressed by a wide range of tissues. Adult myogen-
ic precursor cells (satellite cells) express both HGF and Met. Following muscle injury, au-
tocrine HGF-Met stimulation plays a key role in promoting activation and early division 
of satellite cells. Magic-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is 
an HGF-derived, engineered protein that contains two Met-binding domains. Magic-
F1 protects myogenic precursors against apoptosis, increasing their fusion ability and 
enhancing skeletal muscle differentiation in transgenic mice [1]. To deeply investigate 
gene expression profiles of wt and Magic-F1 satellite cells, microarray analysis has been 
performed. We described here the preliminary results of microarray analysis focusing 
on muscular hypertrophy and vasculogenesis gene signatures in Magic-F1 transgenic 
mice. In parallel we performed an in vivo analysis on hemizygous and homozygous 
Magic-F1 transgenic mice that displayed constitutive muscular hypertrophy, improving 
running performance and accelerating muscle regeneration following injury. Previous 
studies show that muscular hypertrophy could positively influence vascular network, 
increasing vessel number in skeletal muscle, because one of the unique features of mam-
malian skeletal muscle is its remarkable ability to adapt to different functional demands 
by changing phenotypic profiles. 
Preliminary data with microarray assay show differences in expression in specific 
genes (growth factors, transcription factors and atrogenes). In particular we observed 
two-fold increase in VEGF, MyoD and MURF. Furthermore VEGF-B, a key regulator for 
vasculogenesis in skeletal and cardiac muscles, showed higher expression in transgenic 
satellite cells respect to the control [2]. Consistently, transgenic mice showed 36,9% in-
crease of muscle capillary network (5 capillaries/fiber on average), in comparison to 
the controls (4 capillaries/fiber). Conversely, we found a lower arterioles (34,34%) and 
venules (77,3%) density in the muscular tissue of the homozygous transgenic mice in 
comparison to the wt. These findings clearly show that Magic-F1 can positively regulate 
vasculogenesis, triggering VEGF signaling and increasing the capillary vessel number.
References
[1] Cassano M et al. (2008) PLoS ONE. 3: e3223.
[2] Lohela M et al. (2009) Curr. Opin. Cell Biol. 21(2):154-65.
Key words
VEGF, vasculogenesis, muscle hypertrophy


Gene signature of muscle hypertrophy

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Gene signature of muscle hypertrophy

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