mDia1 and Cdc42 regulate Activin B-induced migration of bone marrow-derived mesenchymal stromal cells,STEM CELLS

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mDia1 and Cdc42 regulate Activin B-induced migration of bone marrow-derived mesenchymal stromal cells
STEM CELLS ( IF 4.0 ) Pub Date : 2018-11-09 , DOI: 10.1002/stem.2924
Xueer Wang ₁ , Pei Tang ₁ , Fukun Guo ₂ , Min Zhang ₁ , Yuan Yan ₁ , Mianbo Huang ₁ , Yinghua Chen ₁ , Lu Zhang ₃ , Lin Zhang ₁

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In a previous study, we have shown that Activin B is a potent chemoattractant for bone marrow‐derived mesenchymal stromal cells (BMSCs). As such, the combination of Activin B and BMSCs significantly accelerated rat skin wound healing. In another study, we showed that RhoA activation plays a key role in Activin B‐induced BMSC migration. However, the role of the immediate downstream effectors of RhoA in this process is unclear. Here, we demonstrated that mammalian homolog of Drosophila diaphanous‐1 (mDia1), a downstream effector of RhoA, exerts a crucial function in Activin B‐induced BMSC migration by promoting membrane ruffling, microtubule morphology, and adhesion signaling dynamics. Furthermore, we showed that Activin B does not change Rac1 activity but increases Cdc42 activity in BMSCs. Inactivation of Cdc42 inhibited Activin B‐stimulated Golgi reorientation and the cell migration of BMSCs. Furthermore, knockdown of mDia1 affected Activin B‐induced BMSC‐mediated wound healing in vivo. In conclusion, this study demonstrated that the RhoA‐mDia1 and Cdc42 pathways regulate Activin B‐induced BMSC migration. This study may help to optimize clinical MSC‐based transplantation strategies to promote skin wound healing. Stem Cells 2019;37:150–161

中文翻译：

mDia1 和 Cdc42 调节激活素 B 诱导的骨髓间充质基质细胞迁移

在之前的一项研究中，我们已经证明 Activin B 是骨髓间充质基质细胞 (BMSC) 的有效化学引诱剂。因此，激活素 B 和 BMSC 的组合显着加速了大鼠皮肤伤口的愈合。在另一项研究中，我们发现 RhoA 激活在激活素 B 诱导的 BMSC 迁移中发挥着关键作用。然而，RhoA 直接下游效应器在此过程中的作用尚不清楚。在这里，我们证明了果蝇 diaphanous-1 (mDia1) 的哺乳动物同源物（RhoA 的下游效应子）通过促进膜皱褶、微管形态和粘附信号动力学，在激活素 B 诱导的 BMSC 迁移中发挥关键功能。此外，我们发现 Activin B 不会改变 BMSC 中的 Rac1 活性，但会增加 Cdc42 活性。 Cdc42 失活抑制激活素 B 刺激的高尔基体重新定向和 BMSC 的细胞迁移。此外，mDia1 的敲低影响了 Activin B 诱导的 BMSC 介导的体内伤口愈合。总之，本研究证明 RhoA-mDia1 和 Cdc42 通路调节激活素 B 诱导的 BMSC 迁移。这项研究可能有助于优化临床基于间充质干细胞的移植策略，以促进皮肤伤口愈合。干细胞 2019；37：150–161

更新日期：2018-11-09

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