Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation
In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum c...
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Wiley
2017-01-01
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Series: | Stem Cells International |
Online Access: | http://dx.doi.org/10.1155/2017/5180579 |
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author | Yun Bin Lee Jong Ho Choi Eun Nam Kim Jin Seok Hyun-Jung Lee Jung-Hwan Yoon Gi Jin Kim |
author_facet | Yun Bin Lee Jong Ho Choi Eun Nam Kim Jin Seok Hyun-Jung Lee Jung-Hwan Yoon Gi Jin Kim |
author_sort | Yun Bin Lee |
collection | DOAJ |
description | In cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism. |
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institution | Kabale University |
issn | 1687-966X 1687-9678 |
language | English |
publishDate | 2017-01-01 |
publisher | Wiley |
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spelling | doaj-art-fd9ddc638d544464a17a9894d4c94b242025-02-03T01:07:27ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/51805795180579Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct LigationYun Bin Lee0Jong Ho Choi1Eun Nam Kim2Jin Seok3Hyun-Jung Lee4Jung-Hwan Yoon5Gi Jin Kim6Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaDepartment of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Republic of KoreaDepartment of Biomedical Science, CHA University, Seongnam, Republic of KoreaIn cholestatic liver diseases, impaired bile excretion disrupts lipid homeostasis. We investigated changes of lipid metabolism, including mitochondrial β-oxidation, in a rat model of bile duct ligation (BDL) in which chorionic plate-derived mesenchymal stem cells (CP-MSCs) were transplanted. Serum cholesterol level, which was elevated after BDL, was significantly decreased following CP-MSC transplantation. The expression levels of genes involved in intracellular lipid uptake, including long-chain fatty acyl-CoA synthetases and fatty acid transport proteins, were decreased in rats after BDL; however, they were not significantly changed by subsequent CP-MSC transplantation. Carnitine palmitoyltransferase 1A (CPT1A), a rate-limiting enzyme in mitochondrial β-oxidation, was upregulated after BDL and then was downregulated after CP-MSC transplantation. CPT1A expression was changed via microRNA-33—a posttranscriptional regulator of CPT1A—in a peroxisome proliferator-activated receptor α-independent manner. Cellular adenosine triphosphate production—an indicator of mitochondrial function—was reduced after BDL and was restored by CP-MSC transplantation. Expression levels of heme oxygenases also were significantly affected following BDL and CP-MSC transplantation. Lipid metabolism is altered in response to chronic cholestatic liver injury and can be restored by CP-MSC transplantation. Our study findings support the therapeutic potential of CP-MSCs in cholestatic liver diseases and help in understanding the fundamental mechanisms by which CP-MSCs affect energy metabolism.http://dx.doi.org/10.1155/2017/5180579 |
spellingShingle | Yun Bin Lee Jong Ho Choi Eun Nam Kim Jin Seok Hyun-Jung Lee Jung-Hwan Yoon Gi Jin Kim Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation Stem Cells International |
title | Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation |
title_full | Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation |
title_fullStr | Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation |
title_full_unstemmed | Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation |
title_short | Human Chorionic Plate-Derived Mesenchymal Stem Cells Restore Hepatic Lipid Metabolism in a Rat Model of Bile Duct Ligation |
title_sort | human chorionic plate derived mesenchymal stem cells restore hepatic lipid metabolism in a rat model of bile duct ligation |
url | http://dx.doi.org/10.1155/2017/5180579 |
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