Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis.
Pretreatment with G-CSF Could Enhance the Antifibrotic Effect of BM-MSCs on Pulmonary Fibrosis.
复制标题
G-CSF预处理可增强BM-MSC对肺纤维化的抗纤维化作用。
DOI：
10.1155/2019/1726743
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Tang S
中科院分区：
文献类型：
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作者：
Zhao F;Liu W;Yue S;Yang L;Hua Q;Zhou Y;Cheng H;Luo Z;Tang S
粒细胞集落刺激因子（G-CSF）可以促进多种受损组织的修复，但其潜在机制尚未完全阐明。骨髓间充质干细胞（BM-MSCs）在受损组织的修复中发挥重要作用。本研究的目的是探讨用G-CSF预处理BM-MSCs是否可以通过上调CXCR 4表达来促进其体外移植后归巢肺的能力，从而潜在地显著增加BM-MSCs的抗纤维化作用。在博来霉素注射后第14天，将用G-CSF预处理的BM-MSC移植到小鼠中。第21天通过病理学检查和胶原含量测定来检测BM-MSCs在小鼠体内的抗纤维化作用。用G-CSF预处理BM-MSCs显著促进其归巢至肺的能力并增强其抗纤维化作用。然而，敲低BM-MSCs中的CXCR 4表达显著抑制了G-CSF促进BM-MSCs迁移和归巢至肺的能力以及由此产生的抗纤维化作用。我们还发现G-CSF显著增加BM-MSCs中CXCR 4表达和AKT磷酸化，并且AKT通路抑制剂LY 294002显著降低G-CSF上调BM-MSCs中CXCR 4表达的能力。用G-CSF预处理BM-MSC通过上调CXCR 4表达促进BM-MSC归巢至肺，导致BM-MSC的抗纤维化作用显著增加。本研究为BM-MSCs在不同组织修复中的应用提供了新的途径。
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.