Galectin-3 Enhances Migration of Minature Pig Bone Marrow Mesenchymal Stem Cells Through Inhibition of RhoA-GTP Activity.
Galectin-3 Enhances Migration of Minature Pig Bone Marrow Mesenchymal Stem Cells Through Inhibition of RhoA-GTP Activity.
复制标题
Galectin-3 通过抑制 RhoA-GTP 活性增强小型猪骨髓间充质干细胞的迁移
DOI：
10.1038/srep26577
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发表时间：
2016-05-24
影响因子：
4.6
通讯作者：
Li K
中科院分区：
文献类型：
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作者：
Gao Q;Xia Y;Liu L;Huang L;Liu Y;Zhang X;Xu K;Wei J;Hu Y;Mu Y;Li K
骨髓间充质干细胞（BM-MSCs）因其具有良好的迁移特性而被广泛应用于组织工程中。然而，BM-MSCs在达到损伤和自我更新方面存在局限性。因此，增强BM-MSC迁移对于治疗应用是重要的。在这里，我们评估了半乳糖凝集素-3（Gal-3）是否增加小型猪BM-MSC的迁移。用短发夹状RNA（shRNA）敲低Gal-3基因或慢病毒载体转染五指山小型猪骨髓间充质干细胞（BM-MSCs）。增殖和迁移实验表明，Gal-3的敲低损害BM-MSC的增殖和迁移，而Gal-3过表达促进这些行为。RhoA-GTP活性在Gal-3 shRNA转染的BM-MSCs中上调，而Rac-1-和Cdc 42-GTP没有变化。Western blotting结果显示Gal-3基因敲除的骨髓间充质干细胞在血清饥饿12 h后p-AKT（ser 473）和p-Erk 12表达下调。血清饥饿6 h后p-AKT（ser 473）表达上调，而p-Erk 1/2表达无变化。用C3转移酶或Y27632处理增强了迁移，而Gal-3敲低损害了处理的细胞的迁移。这些结果表明Gal-3可能通过抑制RhoA-GTP活性、增加p-AKT（ser 473）表达和调节p-Erk 1/2水平而促进BM-MSC迁移。我们的研究表明Gal-3在调节小型猪BM-MSC迁移中具有新的功能，这可能有利于治疗应用。
Bone marrow mesenchymal stem cells (BM-MSCs) are used in tissue engineering because of their migration characters. However, BM-MSCs have limitations in terms of reaching injuries and self-renewal. Therefore, enhancement of BM-MSC migration is important for therapeutic applications. Here, we assessed whether galectin-3 (Gal-3) increases the migration of minature pig BM-MSCs. Gal-3 was knocked down by short hairpin RNA (shRNA) or overexpressed using a lentiviral vector in Wuzhishan minature pig BM-MSCs. Proliferation and migration assays showed that knockdown of Gal-3 impaired BM-MSC proliferation and migration, whereas Gal-3 overexpression promoted these behaviors. RhoA-GTP activity was upregulated in Gal-3 shRNA-transfected BM-MSCs, while Rac-1- and Cdc42-GTP showed no changes. Western blotting indicated downregulation of p-AKT (ser473) and p-Erk1/2 after serum starvation for 12 h in Gal-3-knockdown BM-MSCs. p-AKT (ser473) expression was upregulated after serum starvation for 6 h and p-Erk1/2 expression was unchanged in Gal-3-overexpressing BM-MSCs. Treatment with C3 transferase or Y27632 enhanced migration, whereas Gal-3 knockdown impaired migration in treated cells. These results demonstrate that Gal-3 may enhance BM-MSC migration, mainly through inhibiting RhoA-GTP activity, increasing p-AKT (ser473) expression and regulating p-Erk1/2 levels. Our study suggests a novel function of Gal-3 in regulating minature pig BM-MSC migration, which may be beneficial for therapeutic applications.