Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 37, Issue 5, Pages 1914-1926Publisher
KARGER
DOI: 10.1159/000438552
Keywords
Sitagliptin; Mesenchymal stem cell; Hypoxia; Apoptosis; Autophagy
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Funding
- China Health St Medical Development Foundation [2011-H25]
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Background/Aims: Dipeptidyl peptidase-4 (DPP-4) inhibitors have pleiotropic effects on cardiovascular protection beyond the antidiabetic property. However, it remains unknown that the impact of one DPP-4 inhibitor sitagliptin on the survival of mesenchymal stem cells (MSCs) in hypoxia and serum deprivation (H/SD) environment. Methods: The apoptosis and autophagy of MSCs were analyzed in different concentrations of sitagliptin under H/SD condition. For later studies, we tested the relationship between anti-apoptotic and anti-autophagic effects of sitagliptin. The level of cell apoptosis was analyzed by Annexin V-FITC/PI staining, western blot of BcI-2 and Bax proteins. Autophagy flux was assessed by multiple autophagy related proteins and substrates. Cell autophagy was identified by acridine orange staining, western blot of Beclin 1 and light chain 3 protein, and transmission electron microscopy. Results: We demonstrated that sitagliptin attenuated hypoxia-induced apoptosis and autophagy of MSCs. Furthermore, sitagliptin regulated cell autophagy by BcI-2/ Beclin 1 pathway in H/SD condition. Conclusions: This study provides insight into the utility of the DPP-4 inhibitor sitagliptin for MSCs transplantation in the ischemic microenvironment that extends its antidiabetic property. (C) 2015 The Author(s) Published by S. Karger AG, Basel
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