期刊
TISSUE & CELL
卷 46, 期 2, 页码 127-135出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.tice.2013.12.006
关键词
Mesenchymal stem cells; Endoderm; Differentiation; AKT; ERK
资金
- Bio AMP
- Medical Technology Development Program of the National Research Foundation (NRF) - Korean government (MEST) [2012M3A9B4028636]
- Industrial Core Technology Development Program - Ministry of Knowledge Economy [10033594]
- National Research Foundation of Korea [2012M3A9B4028636, 21A20132112574] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Mesenchymal stem cells (MSCs) are mesoderm-derived cells that are considered a good source of somatic cells for treatment of many degenerative diseases. Previous studies have reported the differentiation of mesodermal MSCs into endodermal and ectodermal cell types beyond their embryonic lineages, including hepatocytes and neurons. However, the molecular pathways responsible for the direct or indirect cell type conversion and the functional ability of the differentiated cells remain unclear and need further research. In the present study, we demonstrated that valproic acid (VPA), which is a histone deacetylase inhibitor, induced an increase in the expression of endodermal genes including CXCR4, SOX17, FOXA1, FOXA2, GSC, c-MET, EOMES, and HNF-1 beta in human umbilical cord derived MSCs (hUCMSCs). In addition, we found that VPA is able to increase these endodermal genes in hUCMSCs by activating signal transduction of AKT and ERK. VPA pretreatment increased hepatic differentiation at the expense of adipogenic differentiation. The effects of VPA on modulating hUCMSCs fate were diminished by blocking AKT and ERK activation using specific signaling inhibitors. Together, our results suggest that VPA contributes to the lineage conversion of hUCMSCs to hepatic cell fate by upregulating the expression of endodermal genes through AKT and ERK activation. (C) 2013 Elsevier Ltd. All rights reserved.
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