title: The biomolecular basis of adipogenic differentiation of adipose-derived stem cells.
abstract: There is considerable attention regarding the role of receptor signaling and downstream-regulated mediators in the homeostasis of adipocytes, but less information is available concerning adipose-derived stem cell (ASC) biology. Recent studies revealed that the pathways regulating ASC differentiation involve the activity of receptor tyrosine kinases (RTKs), including fibroblast growth factor, vascular endothelial growth factor, ErbB receptors and the downstream-regulated serine/threonine protein kinase B (Akt) and phosphatase and tensin homolog (PTEN) activity. RTKs are cell surface receptors that represent key regulators of cellular homeostasis but also play a critical role in the progression of cancer. Many of the metabolic effects and other consequences of activated RTKs are mediated by the modulation of Akt and extracellular signal-regulated protein kinases 1 (Erk-1) signaling. Akt activity sustains survival and the adipogenic differentiation of ASCs, whereas Erk-1 appears downregulated. The inhibition of FGFR-1, EGFR and ErbB2 reduced proliferation, but only FGFR-1 inihibition reduced Akt activity and adipogenesis. Adipogenesis and neovascularization are also chronologically and spatially coupled processes and RTK activation and downstream targets are also involved in ASC-mediated angiogenesis. The potentiality of ASCs and the possibility to modulate specific molecular pathways underlying ASC biological processes and, in particular, those shared with cancer cells, offer new exciting strategies in the field of regenerative medicine.
authors.affiliation: Institute of Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy. scioli@med.uniroma2.it.
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Scioli
authors.affiliation: Institute of Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy. alessandrabielli@hotmail.it.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bielli
authors.affiliation: Institute of Plastic Surgery, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy. pietrogentile2004@libero.it.
authors.forename: Pietro
authors.initials: P
authors.lastname: Gentile
authors.affiliation: Institute of Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy. donatella.mazzaglia@hotmail.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Mazzaglia
authors.affiliation: Institute of Plastic Surgery, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy. valeriocervelli@virgilio.it.
authors.forename: Valerio
authors.initials: V
authors.lastname: Cervelli
authors.affiliation: Institute of Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy. orlandi@uniroma2.it.
authors.forename: Augusto
authors.initials: A
authors.lastname: Orlandi
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3
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