15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway
It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma...
Saved in:
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Wiley
2015-01-01
|
Series: | PPAR Research |
Online Access: | http://dx.doi.org/10.1155/2015/876160 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
_version_ | 1832556037818810368 |
---|---|
author | Xin Liu Shuangshuang Jia Weiyang Li Le Yang Lin Yang Lin Wang Liying Li |
author_facet | Xin Liu Shuangshuang Jia Weiyang Li Le Yang Lin Yang Lin Wang Liying Li |
author_sort | Xin Liu |
collection | DOAJ |
description | It has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARγ), is considered a new inhibitor of cell migration. However, the actions of 15d-PGJ2 on BMSC migration remain unknown. In this study, we investigated the effects of 15d-PGJ2 on the migration of BMSCs using a mouse model of chronic liver fibrosis and primary mouse BMSCs. Our results demonstrated that in vivo, 15d-PGJ2 administration inhibited the homing of BMSCs to injured liver by flow cytometric analysis and, in vitro, 15d-PGJ2 suppressed primary BMSC migration in a dose-dependent manner determined by Boyden chamber assay. Furthermore, the repressive effect of 15d-PGJ2 was blocked by reactive oxygen species (ROS) inhibitor, but not PPARγ antagonist, and action of 15d-PGJ2 was not reproduced by PPARγ synthetic ligands. In addition, 15d-PGJ2 triggered a significant ROS production and cytoskeletal remodeling in BMSCs. In conclusion, our results suggest that 15d-PGJ2 plays a crucial role in homing of BMSCs to the injured liver dependent on ROS production, independently of PPARγ, which may represent a new strategy in the treatment of liver fibrosis. |
format | Article |
id | doaj-art-06a96b18e10843aa820200abecb61256 |
institution | Kabale University |
issn | 1687-4757 1687-4765 |
language | English |
publishDate | 2015-01-01 |
publisher | Wiley |
record_format | Article |
series | PPAR Research |
spelling | doaj-art-06a96b18e10843aa820200abecb612562025-02-03T05:46:26ZengWileyPPAR Research1687-47571687-47652015-01-01201510.1155/2015/87616087616015-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox PathwayXin Liu0Shuangshuang Jia1Weiyang Li2Le Yang3Lin Yang4Lin Wang5Liying Li6Department of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaDepartment of Cell Biology, Municipal Laboratory for Liver Protection and Regulation of Regeneration, Capital Medical University, Beijing 100069, ChinaIt has been reported that bone marrow-derived mesenchymal stem cells (BMSCs) have capacity to migrate to the damaged liver and contribute to fibrogenesis in chronic liver diseases. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARγ), is considered a new inhibitor of cell migration. However, the actions of 15d-PGJ2 on BMSC migration remain unknown. In this study, we investigated the effects of 15d-PGJ2 on the migration of BMSCs using a mouse model of chronic liver fibrosis and primary mouse BMSCs. Our results demonstrated that in vivo, 15d-PGJ2 administration inhibited the homing of BMSCs to injured liver by flow cytometric analysis and, in vitro, 15d-PGJ2 suppressed primary BMSC migration in a dose-dependent manner determined by Boyden chamber assay. Furthermore, the repressive effect of 15d-PGJ2 was blocked by reactive oxygen species (ROS) inhibitor, but not PPARγ antagonist, and action of 15d-PGJ2 was not reproduced by PPARγ synthetic ligands. In addition, 15d-PGJ2 triggered a significant ROS production and cytoskeletal remodeling in BMSCs. In conclusion, our results suggest that 15d-PGJ2 plays a crucial role in homing of BMSCs to the injured liver dependent on ROS production, independently of PPARγ, which may represent a new strategy in the treatment of liver fibrosis.http://dx.doi.org/10.1155/2015/876160 |
spellingShingle | Xin Liu Shuangshuang Jia Weiyang Li Le Yang Lin Yang Lin Wang Liying Li 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway PPAR Research |
title | 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway |
title_full | 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway |
title_fullStr | 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway |
title_full_unstemmed | 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway |
title_short | 15-Deoxy-Δ12,14-Prostaglandin J2 Inhibits Homing of Bone Marrow-Derived Mesenchymal Stem Cells Triggered by Chronic Liver Injury via Redox Pathway |
title_sort | 15 deoxy δ12 14 prostaglandin j2 inhibits homing of bone marrow derived mesenchymal stem cells triggered by chronic liver injury via redox pathway |
url | http://dx.doi.org/10.1155/2015/876160 |
work_keys_str_mv | AT xinliu 15deoxyd1214prostaglandinj2inhibitshomingofbonemarrowderivedmesenchymalstemcellstriggeredbychronicliverinjuryviaredoxpathway AT shuangshuangjia 15deoxyd1214prostaglandinj2inhibitshomingofbonemarrowderivedmesenchymalstemcellstriggeredbychronicliverinjuryviaredoxpathway AT weiyangli 15deoxyd1214prostaglandinj2inhibitshomingofbonemarrowderivedmesenchymalstemcellstriggeredbychronicliverinjuryviaredoxpathway AT leyang 15deoxyd1214prostaglandinj2inhibitshomingofbonemarrowderivedmesenchymalstemcellstriggeredbychronicliverinjuryviaredoxpathway AT linyang 15deoxyd1214prostaglandinj2inhibitshomingofbonemarrowderivedmesenchymalstemcellstriggeredbychronicliverinjuryviaredoxpathway AT linwang 15deoxyd1214prostaglandinj2inhibitshomingofbonemarrowderivedmesenchymalstemcellstriggeredbychronicliverinjuryviaredoxpathway AT liyingli 15deoxyd1214prostaglandinj2inhibitshomingofbonemarrowderivedmesenchymalstemcellstriggeredbychronicliverinjuryviaredoxpathway |