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缺氧通过 HIF-1α 信号改变间充质干细胞的趋化行为。

Hypoxia changes chemotaxis behaviour of mesenchymal stem cells via HIF-1α signalling.

机构信息

Department of Orthopedic Surgery, TongRen Hospital, School of Medicine, Shanghai JiaoTong University, Shanghai, China.

出版信息

J Cell Mol Med. 2019 Mar;23(3):1899-1907. doi: 10.1111/jcmm.14091. Epub 2019 Jan 9.

Abstract

Mesenchymal stem cells (MSCs) have drawn great attention because of their therapeutic potential. It has been suggested that intra-venous infused MSCs could migrate the site of injury to help repair the damaged tissue. However, the mechanism for MSC migration is still not clear so far. In this study, we reported that hypoxia increased chemotaxis migration of MSCs. At 4 and 6 hours after culturing in hypoxic (1% oxygen) conditions, the number of migrated MSCs was significantly increased. Meanwhile, hypoxia also increased the expression of HIF-1α and SDF-1. Using small interference RNA, we knocked down the expression of HIF-1α in MSCs to study the role of HIF-1α in hypoxia induced migration. Our data indicated that knocking down the expression of HIF-1α not only abolished the migration of MSCs, but also reduced the expression of SDF-1. Combining the results of migration assay and expression at RNA and protein level, we demonstrated a novel mechanism that controls the increase of MSCs migration. This mechanism involved HIF-1α mediated SDF-1 expression. These findings provide new insight into the role of HIF-1α in the hypoxia induced MSC migration and can be a benefit for the development of MSC-based therapeutics for wound healing.

摘要

间充质干细胞(MSCs)因其治疗潜力而受到广泛关注。有研究表明,静脉输注的 MSCs 可以迁移到损伤部位,帮助修复受损组织。然而,MSC 迁移的机制至今仍不清楚。在本研究中,我们报道了缺氧可增加 MSCs 的趋化性迁移。在缺氧(1%氧气)条件下培养 4 和 6 小时后,迁移的 MSCs 数量明显增加。同时,缺氧还增加了 HIF-1α 和 SDF-1 的表达。通过小干扰 RNA,我们敲低了 MSCs 中 HIF-1α 的表达,以研究 HIF-1α 在缺氧诱导的迁移中的作用。我们的数据表明,敲低 HIF-1α 的表达不仅消除了 MSCs 的迁移,还降低了 SDF-1 的表达。结合迁移实验和 RNA 及蛋白水平的表达结果,我们证明了一种新的调控机制,可控制 MSCs 迁移的增加。该机制涉及 HIF-1α 介导的 SDF-1 表达。这些发现为 HIF-1α 在缺氧诱导的 MSC 迁移中的作用提供了新的认识,并有助于开发基于 MSC 的创伤愈合治疗方法。

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