Epigenetic Alterations of IL-6/STAT3 Signaling by Placental Stem Cells Promote Hepatic Regeneration in a Rat Model with CCl4-induced Liver Injury
- Authors
- Jung, Jieun; Moon, Ji Wook; Choi, Jong-Ho; Lee, Yong Woo; Park, Sun-Hwa; Kim, Gi Jin
- Issue Date
- 5월-2015
- Publisher
- KOREAN SOC STEM CELL RESEARCH
- Keywords
- DNA methylation; IL-6 signaling; Liver regeneration; Placenta stem cells; Transplantation routes
- Citation
- INTERNATIONAL JOURNAL OF STEM CELLS, v.8, no.1, pp.79 - 89
- Indexed
- SCOPUS
- Journal Title
- INTERNATIONAL JOURNAL OF STEM CELLS
- Volume
- 8
- Number
- 1
- Start Page
- 79
- End Page
- 89
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/93743
- DOI
- 10.15283/ijsc.2015.8.1.79
- ISSN
- 2005-3606
- Abstract
- Background: Human chorionic plate-derived mesenchymal stem cells (CP-MSCs) isolated from the placenta have been reported to demonstrate therapeutic effects in animal models of liver injury; however, the underlying epigenetic mechanism of this effect has not been elucidated. Thus, we investigated whether CP-MSCs influence epigenetic processes during regeneration of the injured liver. Methods: CP-MSCs were engrafted into a carbon tetrachloride (CCl4)-injured rat model through direct transplantation into the liver (DTX), intrasplenic transplantation (STX), and intravenous transplantation via the tail vein (TTX). Non-transplanted (NTX) rats were maintained as sham controls. Liver tissues were analyzed after transplantation using immunohistochemistry, western blot analysis, and quantitative methylation-specific polymerase chain reaction. Proliferation and human interleukin-6 (hIL-6) enzyme-linked immunosorbent assays were performed using CCl4-treated hepatic cells that were co-cultured with CP-MSCs. Results: The Ki67 labeling index, cell cyclins, albumin, IL-6, and gp130 levels were elevated in the CP-MSC transplantation groups. The concentration of hIL-6 in supernatants and the proliferation of CCl4-treated rat hepatic cells were enhanced by co-culturing with CF-MSCs (p < 0.05), while the methylation of IL-6/IL-6R and STAT3 by CP-MSC transplantation decreased. Conclusion: These results suggest that administration of CP-MSCs promotes IL-6/STAT3 signaling by decreasing the methylation of the IL-6/SATA3 promoters and thus inducing the proliferation of hepatic cells in a CCl4-injured liver rat model. These data advance our understanding of the therapeutic mechanisms. in injured livers, and can facilitate the development of cell-based therapies using placenta-derived stem cells.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.