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Gene expression profiling of HGF/Met activation in neonatal mouse heart

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Abstract

Hepatocyte Growth Factor (HGF) controls growth and differentiation in different cell types, including cardiac cells. However, its downstream effectors are poorly understood. To investigate the transcriptional targets of HGF, we analyzed the hearts of neonatal mice with cardiomyocyte-specific HGF overexpression with whole genome DNA microarrays. When comparing HGF expressing versus control hearts, we found a total of 249 transcripts with significant gene expression changes (210 upregulated and 39 downregulated). Gene Ontology (GO) annotation analysis revealed that the transcripts modulated by HGF were enriched for metabolic functions including: protein translation, vesicle-mediated transport, regulation of transcription, regulation of muscle development. Using an automated literature meta-analysis approach, we obtained a co-occurrence network oriented to the positive regulatory role of Myc and Notch1 in controlling some of the genes which are downstream to HGF. GO analysis of this network returned genes involved in the regulation of heart development. HGF positively controls MyocD, an activator of cardiac gene expression, and Hdac5, an inhibitor of cardiac growth. These results may unveil a new role of HGF in the modulation of signaling pathways implicated in the activation or repression of cardiomyogenesis.

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Acknowledgments

We gratefully acknowledge Alice Poli for technical help in ProteinQuest. We kindly acknowledge the constant support of the Association Francaise contre les Myopathies (AFM) and the Seventh Framework Programme (FP7). V.S. was a Fellow of Universita` Italo Francese in 2011 (UIF, Cap. III Progetto Vinci 2008). Fellowships of V.S. and C.L. are granted by FP7-2010-ICT-GC “EM-SAFETY” project n. 265772.

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Authors and Affiliations

  1. Department of Oncology, University of Turin, Turin, Italy

    Stefano Gatti, Christian Leo, Simona Gallo, Valentina Sala, Enzo Medico & Tiziana Crepaldi

  2. BioDigitalValley, Pont Saint Martin (AO), Italy

    Enrico Bucci & Massimo Natale

  3. Laboratory of Oncogenomics, Institute for Cancer Research and Treatment, Candiolo, Italy

    Daniela Cantarella & Enzo Medico

  4. Department of Oncology, Corso M. D’Azeglio 52, 10126, Turin, Italy

    Tiziana Crepaldi

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  1. Stefano Gatti
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Correspondence to Tiziana Crepaldi.

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Gatti, S., Leo, C., Gallo, S. et al. Gene expression profiling of HGF/Met activation in neonatal mouse heart. Transgenic Res 22, 579–593 (2013). https://doi.org/10.1007/s11248-012-9667-2

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