Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis

Granulocyte colony-stimulating factor (G-CSF) can promote the repair of a variety of damaged tissues, but the underlying mechanisms have not yet been fully elucidated. Bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the repair of damaged tissue. The aim of this study was to ex...

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Main Authors: Feiyan Zhao, Wei Liu, Shaojie Yue, Lei Yang, Qingzhong Hua, Yan Zhou, Haipeng Cheng, Ziqiang Luo, Siyuan Tang
Format: Article
Language:English
Published: Wiley 2019-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2019/1726743
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author Feiyan Zhao
Wei Liu
Shaojie Yue
Lei Yang
Qingzhong Hua
Yan Zhou
Haipeng Cheng
Ziqiang Luo
Siyuan Tang
author_facet Feiyan Zhao
Wei Liu
Shaojie Yue
Lei Yang
Qingzhong Hua
Yan Zhou
Haipeng Cheng
Ziqiang Luo
Siyuan Tang
author_sort Feiyan Zhao
collection DOAJ
description Granulocyte colony-stimulating factor (G-CSF) can promote the repair of a variety of damaged tissues, but the underlying mechanisms have not yet been fully elucidated. Bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the repair of damaged tissue. The aim of this study was to explore whether pretreating BM-MSCs with G-CSF can promote their ability of homing to the lung after in vitro transplantation via upregulating the CXCR4 expression, potentially markedly increasing the antifibrotic effect of BM-MSCs. The BM-MSCs pretreated with G-CSF were transplanted into a mouse on day 14 after bleomycin injection. The antifibrotic effects of BM-MSCs in mice were tested on day 21 by using pathological examination and collagen content assay. Pretreatment of BM-MSCs with G-CSF significantly promoted their ability of homing to the lung and enhanced their antifibrotic effects. However, knocking down the CXCR4 expression in BM-MSCs significantly inhibited the ability of G-CSF to promote the migration and homing of BM-MSCs to the lung and the resulting antifibrotic effects. We also found that G-CSF significantly increased the CXCR4 expression and AKT phosphorylation in BM-MSCs, and the AKT pathway inhibitor LY294002 significantly diminished the ability of G-CSF to upregulate the CXCR4 expression in BM-MSCs. Pretreatment of BM-MSCs with G-CSF promotes the homing of BM-MSCs to the lung via upregulating the CXCR4 expression, leading to a marked increase in the antifibrotic effects of BM-MSCs. This study provides new avenues for the application of BM-MSCs in the repair of different tissues.
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spelling doaj-art-10f1ad17b3144c16a44fe7c5c94e91dc2025-02-03T01:00:00ZengWileyStem Cells International1687-966X1687-96782019-01-01201910.1155/2019/17267431726743Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary FibrosisFeiyan Zhao0Wei Liu1Shaojie Yue2Lei Yang3Qingzhong Hua4Yan Zhou5Haipeng Cheng6Ziqiang Luo7Siyuan Tang8Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, ChinaXiangya Nursing School, Central South University, Changsha, Hunan, ChinaDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaCollege of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, ChinaXiangya Nursing School, Central South University, Changsha, Hunan, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, ChinaDepartment of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, ChinaXiangya Nursing School, Central South University, Changsha, Hunan, ChinaGranulocyte colony-stimulating factor (G-CSF) can promote the repair of a variety of damaged tissues, but the underlying mechanisms have not yet been fully elucidated. Bone marrow mesenchymal stem cells (BM-MSCs) play an important role in the repair of damaged tissue. The aim of this study was to explore whether pretreating BM-MSCs with G-CSF can promote their ability of homing to the lung after in vitro transplantation via upregulating the CXCR4 expression, potentially markedly increasing the antifibrotic effect of BM-MSCs. The BM-MSCs pretreated with G-CSF were transplanted into a mouse on day 14 after bleomycin injection. The antifibrotic effects of BM-MSCs in mice were tested on day 21 by using pathological examination and collagen content assay. Pretreatment of BM-MSCs with G-CSF significantly promoted their ability of homing to the lung and enhanced their antifibrotic effects. However, knocking down the CXCR4 expression in BM-MSCs significantly inhibited the ability of G-CSF to promote the migration and homing of BM-MSCs to the lung and the resulting antifibrotic effects. We also found that G-CSF significantly increased the CXCR4 expression and AKT phosphorylation in BM-MSCs, and the AKT pathway inhibitor LY294002 significantly diminished the ability of G-CSF to upregulate the CXCR4 expression in BM-MSCs. Pretreatment of BM-MSCs with G-CSF promotes the homing of BM-MSCs to the lung via upregulating the CXCR4 expression, leading to a marked increase in the antifibrotic effects of BM-MSCs. This study provides new avenues for the application of BM-MSCs in the repair of different tissues.http://dx.doi.org/10.1155/2019/1726743
spellingShingle Feiyan Zhao
Wei Liu
Shaojie Yue
Lei Yang
Qingzhong Hua
Yan Zhou
Haipeng Cheng
Ziqiang Luo
Siyuan Tang
Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis
Stem Cells International
title Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis
title_full Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis
title_fullStr Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis
title_full_unstemmed Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis
title_short Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis
title_sort pretreatment with g csf could enhance the antifibrotic effect of bm mscs on pulmonary fibrosis
url http://dx.doi.org/10.1155/2019/1726743
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