title: Gene expression profiling of HGF/Met activation in neonatal mouse heart.
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.
authors.affiliation: Department of Oncology, University of Turin, Turin, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gatti
authors.forename: Christian
authors.initials: C
authors.lastname: Leo
authors.forename: Simona
authors.initials: S
authors.lastname: Gallo
authors.forename: Valentina
authors.initials: V
authors.lastname: Sala
authors.forename: Enrico
authors.initials: E
authors.lastname: Bucci
authors.forename: Massimo
authors.initials: M
authors.lastname: Natale
authors.forename: Daniela
authors.initials: D
authors.lastname: Cantarella
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.forename: Tiziana
authors.initials: T
authors.lastname: Crepaldi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004318:Doxycycline / Q000494:pharmacology; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D016259:Genes, myc; D006321:Heart / Q000502:physiology*; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000502:physiology; D018995:Myosin Heavy Chains / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D000099251:Myocardin
chemical_list: D004318:Doxycycline; D017228:Hepatocyte Growth Factor; D018995:Myosin Heavy Chains; D009687:Nuclear Proteins; D019859:Proto-Oncogene Proteins c-met; D051881:Receptor, Notch1; D015534:Trans-Activators; D000099251:Myocardin; C553307:HGF protein, mouse; C584019:Myh6 protein, mouse; C497762:Notch1 protein, mouse