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Journal of Cellular Biochemistry

Increased SCF/c-kit by hypoxia promotes autophagy of human placental chorionic plate-derived mesenchymal stem cells via regulating the phosphorylation of mTOR§

Authors

  • Youjin Lee,

    1. Department of Biomedical Science, CHA University, 606-16 Yeoksam1-dong, Kangnam-Gu, Seoul 135-097, Republic of Korea
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  • Jieun Jung,

    1. Department of Biomedical Science, CHA University, 606-16 Yeoksam1-dong, Kangnam-Gu, Seoul 135-097, Republic of Korea
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  • Kyung Jin Cho,

    1. Department of Biomedical Science, College of Health Science, Korea University, 1 JeongReung-Dong, SungBuk-Gu, Seoul 136-703, Republic of Korea
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  • Seoung-Kwan Lee,

    1. Department of Biomedical Science, College of Health Science, Korea University, 1 JeongReung-Dong, SungBuk-Gu, Seoul 136-703, Republic of Korea
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  • Jong-Wan Park,

    1. Department of Pharmacology, Ischemic/Hypoxic Disease Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Republic of Korea
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  • IL-Hoan Oh,

    1. Department of Medical Lifescience, Catholic High Performance Cell Therapy Center, The Catholic University of Korea, 505, Banpo-dong, Seocho-Ku, Seoul 137-701, Republic of Korea
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  • Gi Jin Kim

    Corresponding author
    1. Department of Biomedical Science, CHA University, 606-16 Yeoksam1-dong, Kangnam-Gu, Seoul 135-097, Republic of Korea
    • Department of Biomedical Science, CHA University, 606-16 Yeoksam1-dong, Kangnam-Gu, Seoul 135-097, Republic of Korea.
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  • Conflict of interest: none declared.

  • 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.

Abstract

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.

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