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Dissertation Moustafa Sayed.pdf (3.63 MB)

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Effects of Na/K-ATPase and Its Ligands on Bone Marrow Mesenchymal Stem Cell Differentiation

Sayed, Moustafa
http://rave.ohiolink.edu/etdc/view?acc_num=mco1396351646

Abstract Details

2014, Doctor of Philosophy (PhD), University of Toledo, College of Medicine.
Reported increases of endogenous ligands for Na/K-ATPase induced during kidney dysfunction and heart failure, as well as the role of Na/K-ATPase signaling function in stem cell differentiation, lead us to conduct this study in order to evaluate whether Na/K-ATPase activation through its ligands and associated signaling functions affect bone marrow mesenchymal stem cells (BMSCs) differentiation capacity. BMSCs were isolated from male Sprague-Dawley rats and cultured as described in the materials and methods chapter. The results revealed that marinobufagenin (MBG), a specific Na/K-ATPase ligand, potentiated rosiglitazone-induced adipogenesis in BMSCs. Meanwhile, it attenuated BMSCs osteogenesis. Mechanistically, we found that MBG increases the protein expression of CCAAT/enhancer binding protein alpha (C/EBPa) through the activation of an extracellular regulated kinase (ERK) signaling pathway, which in turn leads to enhanced rosiglitazone-induced adipogenesis. The effect of MBG on C/EBPa expression and on rosiglitazone-induced adipogenesis was blocked by the inhibition of the activation of ERK through use of the inhibitor U0126. Reciprocally, MBG reduced runt-related transcription factor 2 (RunX2) expression which resulted in the inhibition of ß-glycerophosphate/ascorbic acid induced osteogenesis. Moreover, MBG potentiated rosiglitazone-induced adipogenesis in 3T3-L1 cells and in mouse BMSCs. In addition, we found that MBG increased the expression of type-1 collagen in rat BMSCs. These results suggest that Na/K-ATPase and its signaling functions are involved in the regulation of BMSCs differentiation.
Jiang Tian (Committee Chair)
Joseph I. Shapiro (Committee Member)
Jiang Liu (Committee Member)
Andrew Beavis (Committee Member)
Lijun Liu (Committee Member)
121 p.
Biomedical Research

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Citations

  • Sayed, M. (2014). Effects of Na/K-ATPase and Its Ligands on Bone Marrow Mesenchymal Stem Cell Differentiation [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1396351646

    APA Style (7th edition)

  • Sayed, Moustafa. Effects of Na/K-ATPase and Its Ligands on Bone Marrow Mesenchymal Stem Cell Differentiation. 2014. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1396351646.

    MLA Style (8th edition)

  • Sayed, Moustafa. "Effects of Na/K-ATPase and Its Ligands on Bone Marrow Mesenchymal Stem Cell Differentiation." Doctoral dissertation, University of Toledo, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=mco1396351646

    Chicago Manual of Style (17th edition)

mco1396351646
663
© 2014, some rights reserved.Creative Commons License Effects of Na/K-ATPase and Its Ligands on Bone Marrow Mesenchymal Stem Cell Differentiation by Moustafa Sayed is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.