Journal of Integrative Natural Science (통합자연과학논문집)

The Basic Science Institute Chosun University (조선대학교 기초과학연구원)
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Effect of Histone Deacetylase Inhibitors on Differentiation of Human Bone Marrow-derived Stem Cells Into Neuron-like Cells

  • Jang, Sujeong (Department of Physiology, Chonnam National University Medical School) ;
  • Park, Seokho (Department of Physiology, Chonnam National University Medical School) ;
  • Cho, Hyong-Ho (Department of Otolaryngology-Head and Neck Surgery, Chonnam National University Medical School) ;
  • Yang, Ung (Department of Horticulture, Asian Pear Research Institute, College of Agriculture and Life Sciences, Chonnam National University) ;
  • Kang, Maru (Department of Defense Science & Technology, Gwangju University) ;
  • Park, Jong-Seong (Department of Physiology, Chonnam National University Medical School) ;
  • Park, Sah-Hoon (Department of Physiology, Chonnam National University Medical School) ;
  • Jeong, Han-Seong (Department of Physiology, Chonnam National University Medical School)
  • Received : 2019.11.18
  • Accepted : 2019.12.18
  • Published : 2019.12.30
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Abstract

Mesenchymal stem cells (MSCs) are known to differentiate into multiple lineages, making neurogenic differentiation an important target in the clinical field. In the present study, we induced the neurogenic differentiation of cells using histone deacetylase (HDAC) inhibitors and studied their mechanisms for further differentiation in vitro. We treated cells with the HDAC inhibitors, MS-275 and NaB; and found that the cells had neuron-like features such as distinct bipolar or multipolar morphologies with branched processes. The mRNA expressions encoding for NEFL, MAP2, TUJ1, OLIG2, and SYT was significantly increased following HDAC inhibitors treatment compared to without HDAC inhibitors; high protein levels of MAP2 and Tuj1 were detected by immunofluorescence staining. We examined the mechanisms of differentiation and found that the Wnt signaling pathway and downstream mitogen-activate protein kinase were involved in neurogenic differentiation of MSCs. Importantly, Wnt4, Wnt5a/b, and Wnt11 protein levels were highly increased after treatment with NaB; signals were activated through the regulation of Dvl2 and Dvl3. Interestingly, NaB treatment increased the levels of JNK and upregulated JNK phosphorylation. After MS-275 treatment, Wnt protein levels were decreased and GSK-3β was phosphorylated. In this cell, HDAC inhibitors controlled the non-canonical Wnt expression by activating JNK phosphorylation and the canonical Wnt signaling by targeting GSK-3β.

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References

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