Conflict of interest: none declared.
Article first published online: 14 NOV 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 1, pages 79–88, January 2013
How to Cite
Lee, Y., Jung, J., Cho, K. J., Lee, S.-K., Park, J.-W., Oh, I.-H. and Kim, G. J. (2013), Increased SCF/c-kit by hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells via regulating the phosphorylation of mTOR. J. Cell. Biochem., 114: 79–88. doi: 10.1002/jcb.24303
Author contribution: Youjin Lee and Jieun Jung: collection and analysis of data, data interpretation, manuscript drafting. Kyung Jin Cho and Seoung-Kwan Lee: data interpretation and analysis of data. Jong-Wan Park: conception and critical discussion. IL-Hoan Oh: conception, financial support, critical discussion. Gi Jin Kim: conception and design, manuscript drafting, financial support, final approval of manuscript.
Youjin Lee and Jieun Jung equally contributed to this work.
- Issue published online: 14 NOV 2012
- Article first published online: 14 NOV 2012
- Accepted manuscript online: 25 JUL 2012 09:18AM EST
- Manuscript Accepted: 17 JUL 2012
- Manuscript Received: 19 MAR 2012
- Korean Government (MEST). Grant Number: KRF-2011-0019610
- BONE MARROW-DERIVED MESENCHYMAL STEM CELLS (BM-MSCs);
- PLACENTAL CHORIONIC PLATE-DERIVED MESENCHYMAL STEM CELLS (CP-MSCs);
- STEM CELL FACTOR (SCF);
Hypoxia triggers physiological and pathological cellular processes, including proliferation, differentiation, and death, in several cell types. Mesenchymal stem cells (MSCs) derived from various tissues have self-renewal activity and can differentiate towards multiple lineages. Recently, it has been reported that hypoxic conditions tip the balance between survival and death by hypoxia-induced autophagy, although the underlying mechanism is not clear. The objectives of this study are to compare the effect of hypoxia on the self-renewal of bone marrow-derived mesenchymal stem cells (BM-MSCs) and placental chorionic plate-derived mesenchymal stem cells (CP-MSCs) and to investigate the regulatory mechanisms of self-renewal in each MSC type during hypoxia. The expression of self-renewal markers (e.g., Oct4, Nanog, Sox2) was assessed in both cell lines. PI3K and stem cell factor (SCF) expression gradually increased in CP-MSCs but were markedly downregulated in BM-MSCs by hypoxia. The phosphorylation of ERK and mTOR was augmented by hypoxia in CP-MSCs compared to control. Also, the expression of LC3 II, a component of the autophagosome and the hoof-shaped autophagosome was detected more rapidly in CP-MSCs than in BM-MSCs under hypoxia. Hypoxia induced the expression of SCF in CP-MSCs and increased SCF/c-kit pathway promotes the self-renewal activities of CP-MSCs via an autocrine/paracrine mechanism that balances cell survival and cell death events by autophagy. These activities occur to a greater extent in CP-MSCs than in BM-MSCs through regulating the phosphorylation of mTOR. These findings will provide useful guidelines for better understanding the function of SCF/c-kit in the self-renewal and autophagy-regulated mechanisms that promote of MSC survival. J. Cell. Biochem. 114: 79–88, 2012. © 2012 Wiley Periodicals, Inc.