Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Xiu, Guanghui, Li, Xiuling, Yin, Yunyu, Li, Jintao, Li, Bingqin, Chen, Xianzhong, Liu, Ping, Sun, Jie, Ling, Bin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563832/
https://www.ncbi.nlm.nih.gov/pubmed/32452221
http://dx.doi.org/10.1177/0963689720929992
_version_ 1783595576261083136
author Xiu, Guanghui
Li, Xiuling
Yin, Yunyu
Li, Jintao
Li, Bingqin
Chen, Xianzhong
Liu, Ping
Sun, Jie
Ling, Bin
author_facet Xiu, Guanghui
Li, Xiuling
Yin, Yunyu
Li, Jintao
Li, Bingqin
Chen, Xianzhong
Liu, Ping
Sun, Jie
Ling, Bin
author_sort Xiu, Guanghui
collection PubMed
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.
format Online
Article
Text
id pubmed-7563832
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher SAGE Publications
record_format MEDLINE/PubMed
spelling pubmed-75638322020-10-26 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 Xiu, Guanghui Li, Xiuling Yin, Yunyu Li, Jintao Li, Bingqin Chen, Xianzhong Liu, Ping Sun, Jie Ling, Bin Cell Transplant Original Article 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. SAGE Publications 2020-05-26 /pmc/articles/PMC7563832/ /pubmed/32452221 http://dx.doi.org/10.1177/0963689720929992 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Xiu, Guanghui
Li, Xiuling
Yin, Yunyu
Li, Jintao
Li, Bingqin
Chen, Xianzhong
Liu, Ping
Sun, Jie
Ling, Bin
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 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
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563832/
https://www.ncbi.nlm.nih.gov/pubmed/32452221
http://dx.doi.org/10.1177/0963689720929992
work_keys_str_mv AT xiuguanghui sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT lixiuling sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT yinyunyu sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT lijintao sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT libingqin sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT chenxianzhong sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT liuping sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT sunjie sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway
AT lingbin sdf1cxcr4augmentsthetherapeuticeffectofbonemarrowmesenchymalstemcellsinthetreatmentoflipopolysaccharideinducedliverinjurybypromotingtheirmigrationthroughpi3kaktsignalingpathway