SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway
Mesenchymal stem cells (MSCs) are thought to have great potential in the therapy of acute liver injury. It is possible that these cells may be regulated by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling axis, which has been shown to promote stem cells migration...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2020-05-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/0963689720929992 |
| _version_ | 1811331580003614720 |
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| author | Guanghui Xiu Xiuling Li Yunyu Yin Jintao Li Bingqin Li Xianzhong Chen Ping Liu Jie Sun Bin Ling |
| author_facet | Guanghui Xiu Xiuling Li Yunyu Yin Jintao Li Bingqin Li Xianzhong Chen Ping Liu Jie Sun Bin Ling |
| author_sort | Guanghui Xiu |
| collection | DOAJ |
| description | Mesenchymal stem cells (MSCs) are thought to have great potential in the therapy of acute liver injury. It is possible that these cells may be regulated by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling axis, which has been shown to promote stem cells migration in the inflammation-associated diseases. However, the effects of SDF-1/CXCR4 axis on the MSCs-transplantation-based treatment for acute liver injury and the underlying mechanisms are largely unknown. In this study, we sought to determine whether SDF-1/CXCR4 would augment the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) by promoting their migration, which may result from activating the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, in a rat acute liver injury model induced by lipopolysaccharide (LPS). We found that BMSCs transplantation markedly attenuated liver injury and improved the survival of LPS-treated rats. Of interest, overexpression of CXCR4 in BMSCs could substantially promote their migration both in vitro and in vivo , and result in even better therapeutic effects. This might be attributed to the activation of PI3K/Akt signaling pathway in BMSCs that is downstream of CXCR4, as demonstrated by the use of the CXCR4 antagonist AMD3100 and PI3K pathway inhibitor LY294002 assays in vitro and in vivo . Together, our results unraveled a novel molecular mechanism for the therapeutic effect of BMSCs for the treatment of acute liver injury, which may shed a new light on the clinical application of BMSCs for acute liver failure. |
| first_indexed | 2024-04-13T16:22:51Z |
| format | Article |
| id | doaj.art-4cb9475483fc4c4a9f6caa83b934a852 |
| institution | Directory Open Access Journal |
| issn | 1555-3892 |
| language | English |
| last_indexed | 2024-04-13T16:22:51Z |
| publishDate | 2020-05-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-4cb9475483fc4c4a9f6caa83b934a8522022-12-22T02:39:51ZengSAGE PublishingCell Transplantation1555-38922020-05-012910.1177/0963689720929992SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling PathwayGuanghui Xiu0Xiuling Li1Yunyu Yin2Jintao Li3Bingqin Li4Xianzhong Chen5Ping Liu6Jie Sun7Bin Ling8 These authors contributed equally to this article These authors contributed equally to this article These authors contributed equally to this article The Institute of Neuroscience, The Kunming Medical University, Kunming, Yunnan Province, China Department of Intensive Care Unit, The Second People’s Hospital of Yunnan Province (The Fourth Affiliated Hospital of Kunming Medical University), Kunming, Yunnan Province, China Department of Intensive Care Unit, The Second People’s Hospital of Yunnan Province (The Fourth Affiliated Hospital of Kunming Medical University), Kunming, Yunnan Province, China Department of Intensive Care Unit, The Second People’s Hospital of Yunnan Province (The Fourth Affiliated Hospital of Kunming Medical University), Kunming, Yunnan Province, China Department of Intensive Care Unit, The Second People’s Hospital of Yunnan Province (The Fourth Affiliated Hospital of Kunming Medical University), Kunming, Yunnan Province, China Department of Intensive Care Unit, The Second People’s Hospital of Yunnan Province (The Fourth Affiliated Hospital of Kunming Medical University), Kunming, Yunnan Province, ChinaMesenchymal stem cells (MSCs) are thought to have great potential in the therapy of acute liver injury. It is possible that these cells may be regulated by the stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor-4 (CXCR4) signaling axis, which has been shown to promote stem cells migration in the inflammation-associated diseases. However, the effects of SDF-1/CXCR4 axis on the MSCs-transplantation-based treatment for acute liver injury and the underlying mechanisms are largely unknown. In this study, we sought to determine whether SDF-1/CXCR4 would augment the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs) by promoting their migration, which may result from activating the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, in a rat acute liver injury model induced by lipopolysaccharide (LPS). We found that BMSCs transplantation markedly attenuated liver injury and improved the survival of LPS-treated rats. Of interest, overexpression of CXCR4 in BMSCs could substantially promote their migration both in vitro and in vivo , and result in even better therapeutic effects. This might be attributed to the activation of PI3K/Akt signaling pathway in BMSCs that is downstream of CXCR4, as demonstrated by the use of the CXCR4 antagonist AMD3100 and PI3K pathway inhibitor LY294002 assays in vitro and in vivo . Together, our results unraveled a novel molecular mechanism for the therapeutic effect of BMSCs for the treatment of acute liver injury, which may shed a new light on the clinical application of BMSCs for acute liver failure.https://doi.org/10.1177/0963689720929992 |
| spellingShingle | Guanghui Xiu Xiuling Li Yunyu Yin Jintao Li Bingqin Li Xianzhong Chen Ping Liu Jie Sun Bin Ling SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway Cell Transplantation |
| title | SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway |
| title_full | SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway |
| title_fullStr | SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway |
| title_full_unstemmed | SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway |
| title_short | SDF-1/CXCR4 Augments the Therapeutic Effect of Bone Marrow Mesenchymal Stem Cells in the Treatment of Lipopolysaccharide-Induced Liver Injury by Promoting Their Migration Through PI3K/Akt Signaling Pathway |
| title_sort | sdf 1 cxcr4 augments the therapeutic effect of bone marrow mesenchymal stem cells in the treatment of lipopolysaccharide induced liver injury by promoting their migration through pi3k akt signaling pathway |
| url | https://doi.org/10.1177/0963689720929992 |
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