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Int. J. Mol. Sci. 2014, 15(4), 6517-6526; doi:10.3390/ijms15046517

The Biomolecular Basis of Adipogenic Differentiation of Adipose-Derived Stem Cells

1
Institute of Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy
2
Institute of Plastic Surgery, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier, 00133 Rome, Italy
*
Author to whom correspondence should be addressed.
Received: 25 February 2014 / Revised: 5 April 2014 / Accepted: 9 April 2014 / Published: 16 April 2014
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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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. View Full-Text
Keywords: adipose-derived stem cells; receptor tyrosine kinases; Akt; Erk-1; proliferation; differentiation; growth factors adipose-derived stem cells; receptor tyrosine kinases; Akt; Erk-1; proliferation; differentiation; growth factors
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Scioli, M.G.; Bielli, A.; Gentile, P.; Mazzaglia, D.; Cervelli, V.; Orlandi, A. The Biomolecular Basis of Adipogenic Differentiation of Adipose-Derived Stem Cells. Int. J. Mol. Sci. 2014, 15, 6517-6526.

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