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Open AccessArticle

Cellular and Molecular Mechanisms Mediated by recPrPC Involved in the Neuronal Differentiation Process of Mesenchymal Stem Cells

1
Laboratory of Experimental Medicine and Environmental Pathology, Rieti University Hub “Sabina Universitas”, 02100 Rieti, Italy
2
Department of Experimental Medicine, "Sapienza" University, 00161 Rome, Italy
3
Department of Science Dentistry and Maxillofacial, “Sapienza” University, 00161 Rome, Italy
4
Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, 67100 L’Aquila, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(2), 345; https://doi.org/10.3390/ijms20020345
Received: 14 December 2018 / Revised: 11 January 2019 / Accepted: 13 January 2019 / Published: 16 January 2019
(This article belongs to the Special Issue Roles of Stem Cells in Nerve Regeneration)
Human Dental Pulp Stem Cells (hDPSCs) represent a type of adult mesenchymal stem cells that have the ability to differentiate in vitro in several lineages such as odontoblasts, osteoblasts, chondrocytes, adipocytes and neurons. In the current work, we used hDPSCs as the experimental model to study the role of recombinant prion protein 23–231 (recPrPC) in the neuronal differentiation process, and in the signal pathway activation of ERK 1/2 and Akt. We demonstrated that recPrPC was able to activate an intracellular signal pathway mediated by extracellular-signal-regulated kinase 1 and 2 (ERK 1/2) and protein kinase B (Akt). Moreover, in order to understand whether endogenous prion protein (PrPC) was necessary to mediate the signaling induced by recPrPC, we silenced PrPC, demonstrating that the presence of endogenous PrPC was essential for ERK 1/2 and Akt phosphorylation. Since endogenous PrPC is a well-known lipid rafts component, we evaluated the role of these structures in the signal pathway induced by recPrPC. Our results suggest that lipid rafts integrity play a key role in recPrPC activity. In fact, lipid rafts inhibitors, such as fumonisin B1 and MβCD, significantly prevented ERK 1/2 and Akt phosphorylation induced by recPrPC. In addition, we investigated the capacity of recPrPC to induce hDPSCs neuronal differentiation process after long-term stimulation through the evaluation of typical neuronal markers expression such as B3-Tubulin, neurofilament-H (NFH) and growth associated protein 43 (GAP43). Accordingly, when we silenced endogenous PrPC, we observed the inhibition of neuronal differentiation induced by recPrPC. The combined data suggest that recPrPC plays a key role in the neuronal differentiation process and in the activation of specific intracellular signal pathways in hDPSCs. View Full-Text
Keywords: cellular prion protein; shed prion protein; recombinant prion protein; prions; lipid rafts; dental pulp-derived stem cells; mesenchymal stem cells; neural stem cells; adult neurogenesis; neuronal differentiation cellular prion protein; shed prion protein; recombinant prion protein; prions; lipid rafts; dental pulp-derived stem cells; mesenchymal stem cells; neural stem cells; adult neurogenesis; neuronal differentiation
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Martellucci, S.; Santacroce, C.; Santilli, F.; Piccoli, L.; Delle Monache, S.; Angelucci, A.; Misasi, R.; Sorice, M.; Mattei, V. Cellular and Molecular Mechanisms Mediated by recPrPC Involved in the Neuronal Differentiation Process of Mesenchymal Stem Cells. Int. J. Mol. Sci. 2019, 20, 345.

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