Zhao Feiyan, Liu Wei, Yue Shaojie, Yang Lei, Hua Qingzhong, Zhou Yan, Cheng Haipeng, Luo Ziqiang, Tang Siyuan
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
College of Veterinary Medicine, Hunan Agricultural University, Changsha, Hunan, China.
Stem Cells Int. 2019 Jan 3;2019:1726743. doi: 10.1155/2019/1726743. eCollection 2019.
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.
粒细胞集落刺激因子（G-CSF）可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起重要作用。本研究的目的是探讨用G-CSF预处理BM-MSCs是否能通过上调CXCR4表达来促进其体外移植后归巢至肺的能力，从而可能显著增强BM-MSCs的抗纤维化作用。在博来霉素注射后第14天，将经G-CSF预处理的BM-MSCs移植到小鼠体内。在第21天，通过病理检查和胶原含量测定来检测BM-MSCs对小鼠的抗纤维化作用。用G-CSF预处理BM-MSCs可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CXCR4表达可显著抑制G-CSF促进BM-MSCs向肺迁移和归巢的能力以及由此产生的抗纤维化作用。我们还发现，G-CSF可显著增加BM-MSCs中CXCR4的表达和AKT磷酸化，而AKT通路抑制剂LY294002可显著削弱G-CSF上调BM-MSCs中CXCR4表达的能力。用G-CSF预处理BM-MSCs可通过上调CXCR4表达促进BM-MSCs归巢至肺，从而显著增强BM-MSCs的抗纤维化作用。本研究为BM-MSCs在不同组织修复中的应用提供了新途径。
