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

Stefano Gatti, Christian Leo, Simona Gallo, Valentina Sala, Enrico Bucci, Massimo Natale, Daniela Cantarella, Enzo Medico, Tiziana Crepaldi

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)579-593
Number of pages15
JournalTransgenic Research
Volume22
Issue number3
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Cardiac muscle
  • Heart development
  • Hepatocyte Growth Factor
  • Met receptor
  • Microarrays
  • System biology

ASJC Scopus subject areas

  • Biotechnology
  • Genetics
  • Agronomy and Crop Science
  • Animal Science and Zoology

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