title: Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation.
abstract: Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin promoting migration, proliferation, and survival in a wide spectrum of cells, can also modulate different biological responses in stem cells, but the mechanisms involved are not completely understood so far. In this context, we show that short-term exposure of mesenchymal stem cells (MSCs) to HGF can induce the activation of its cognate Met receptor and the downstream effectors ERK1/2, p38MAPK, and PI3K/Akt, while long-term exposure to HGF resulted in cytoskeletal rearrangement, cell migration, and marked inhibition of proliferation through the arrest in the G1-S checkpoint. When added to MSCs, the K252A tyrosine kinase inhibitor prevented HGF-induced responses. HGF's effect on MSC proliferation was reversed by p38 inhibitor SB203580, while the effects on cell migration were abrogated by PI3K inhibitor Wortmannin, suggesting that HGF acts through different pathways to determine its complex effects on MSCs. Prolonged treatment with HGF induced the expression of cardiac-specific markers (GATA-4, MEF2C, TEF1, desmin, alpha-MHC, beta-MHC, and nestin) with the concomitant loss of the stem cell markers nucleostemin, c-kit, and CD105.
authors.affiliation: Molecular and Cellular Lab, Dipartimento di Medicina Interna, Università di Roma Tor Vergata, Via Montpellier, 1, 00133 Roma, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Forte
authors.forename: Marilena
authors.initials: M
authors.lastname: Minieri
authors.forename: Paolo
authors.initials: P
authors.lastname: Cossa
authors.forename: Daniele
authors.initials: D
authors.lastname: Antenucci
authors.forename: Marilena
authors.initials: M
authors.lastname: Sala
authors.forename: Viola
authors.initials: V
authors.lastname: Gnocchi
authors.forename: Roberta
authors.initials: R
authors.lastname: Fiaccavento
authors.forename: Felicia
authors.initials: F
authors.lastname: Carotenuto
authors.forename: Paolo
authors.initials: P
authors.lastname: De Vito
authors.forename: Patrizia Morena
authors.initials: PM
authors.lastname: Baldini
authors.forename: Maria
authors.initials: M
authors.lastname: Prat
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Nardo
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006321:Heart / Q000502:physiology; D017228:Hepatocyte Growth Factor / Q000378:metabolism / Q000494:pharmacology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D010641:Phenotype; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases