Open AccessmDia1 and Cdc42 Regulate Activin B‐Induced Migration of Bone Marrow‐Derived Mesenchymal Stromal Cells
Author(s) -
Wang Xueer,
Tang Pei,
Guo Fukun,
Zhang Min,
Yan Yuan,
Huang Mianbo,
Chen Yinghua,
Zhang Lu,
Zhang Lin
Publication year - 2019
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.2924
Subject(s) - rhoa , microbiology and biotechnology , mesenchymal stem cell , cdc42 , wound healing , stromal cell , biology , cell migration , cancer research , immunology , cell , signal transduction , genetics
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