RhoA regulates Activin B-induced stress fiber formation and migration of bone marrow-derived mesenchymal stromal cell through distinct signaling

Wang, Xueer; Tang, Pei Song; Guo, Fukun; Zhang, Min; Chen, Yinghua; Yan, Yuan; Zhang, Tian; Xu, Ping; Zhang, Lei; Zhang, Lu

doi:10.1016/j.bbagen.2016.09.027

Cited by 10 publications

(18 citation statements)

References 32 publications

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“…In a further study, we demonstrated that although RhoA was important for both Activin B-induced stress fiber formation and the cell movement of BMSCs, ROCK promoted stress fiber formation but suppressed BMSC migration [11]. These findings suggest that stress fiber formation is not likely to count for Activin B-induced BMSC migration and that RhoA regulates Activin Binduced stress fiber formation dependent on ROCK but cell migration independent of ROCK in BMSCs [11]. Therefore, in this study, we explored other downstream effectors of RhoA and other mechanisms for their potential role in BMSC migration induced by Activin B.…”

Section: Introductionmentioning

confidence: 80%

“…Rho-associated protein kinase (ROCK) and mammalian homolog of Drosophila diaphanous-1 (mDia1) are two major effector proteins of RhoA [10]. In a further study, we demonstrated that although RhoA was important for both Activin B-induced stress fiber formation and the cell movement of BMSCs, ROCK promoted stress fiber formation but suppressed BMSC migration [11]. These findings suggest that stress fiber formation is not likely to count for Activin B-induced BMSC migration and that RhoA regulates Activin Binduced stress fiber formation dependent on ROCK but cell migration independent of ROCK in BMSCs [11].…”

Section: Introductionmentioning

confidence: 84%

“…BMSC isolation was performed as previously described [6,11,12]. In brief, MSCs were isolated from the bone marrow of 6-week-old male Sprague-Dawley rats, which were purchased from the Laboratory Animal Centre of Southern Medical University.…”

Section: Isolation Culture and Identification Of Bmscsmentioning

confidence: 99%

“…The cell pellet was resuspended in complete medium (Dulbecco's modified Eagle's medium [DMEM] with 10% fetal bovine serum [FBS] and 1% antibiotic antimycotic solution) and cultured in 100-mm dishes at 37 C and 5% CO 2 . Isolated BMSCs were characterized by immunocytochemistry as we previously described [6,11]. Cells at passages 3-4 were used for all experiments.…”

Section: Isolation Culture and Identification Of Bmscsmentioning

confidence: 99%

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mDia1 and Cdc42 Regulate Activin B-Induced Migration of Bone Marrow-Derived Mesenchymal Stromal Cells

et al. 2018

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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 SIGNIFICANCE STATEMENT This study demonstrates that the RhoA-mDia1 pathway exerts a crucial function in Activin B-induced bone marrow-derived mesenchymal stromal cell (BMSC) migration by regulating membrane ruffle formation, microtubule morphology, and focal adhesion signaling dynamics. Cdc42 regulates Activin B-induced Golgi reorientation at the leading edge of moving BMSCs. Knockdown of mDia1 affects Activin B-induced BMSC-mediated wound healing in vivo. This study has revealed new molecular mechanisms of BMSC migration that will help optimize MSCbased transplantation strategies in clinical skin wound healing.

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Section: Introductionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 84%

Section: Isolation Culture and Identification Of Bmscsmentioning

confidence: 99%

Section: Isolation Culture and Identification Of Bmscsmentioning

confidence: 99%

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mDia1 and Cdc42 Regulate Activin B-Induced Migration of Bone Marrow-Derived Mesenchymal Stromal Cells

et al. 2018

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“…Cells were then plated evenly on 6‐well plates with α‐minimum essential medium (α‐MEM; Gibco BRL) supplemented with 20% foetal bovine serum (FBS; Gibco BRL). Recombinant Mouse activin B Protein (R&D systems, 8260‐AB) was applied to culture medium in IANx group after cells adhesion at 10 ng/mL as recommended 20 …”

Section: Methodsmentioning

confidence: 99%

Sensory nerve‐deficient microenvironment impairs tooth homeostasis by inducing apoptosis of dental pulp stem cells

et al. 2020

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Objectives:The aim of this study is to investigate the role of sensory nerve in tooth homeostasis and its effect on mesenchymal stromal/stem cells (MSCs) in dental pulp. Materials and methods:We established the rat denervated incisor models to identify the morphological and histological changes of tooth. The groups were as follows:IANx (inferior alveolar nerve section), SCGx (superior cervical ganglion removal), IANx + SCGx and Sham group. The biological behaviour of dental pulp stromal/ stem cells (DPSCs) was evaluated. Finally, we applied activin B to DPSCs from sensory nerve-deficient microenvironment to analyse the changes of proliferation and apoptosis. Results: Incisor of IANx and IANx + SCGx groups exhibited obvious disorganized tooth structure, while SCGx group only showed slight decrease of dentin thickness, implying sensory nerve, not sympathetic nerve, contributes to the tooth homeostasis. Moreover, we found sensory nerve injury led to disfunction of DPSCs via activin B/SMAD2/3 signalling in vitro. Supplementing activin B promoted proliferation and reduced apoptosis of DPSCs in sensory nerve-deficient microenvironment. Conclusions: This research first demonstrates that sensory nerve-deficient microenvironment impairs tooth haemostasis by inducing apoptosis of DPSCs via activin B/ SMAD2/3 signalling. Our study provides the evidence for the crucial role of sensory nerve in tooth homeostasis.

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Whole‐blood dysregulation of actin‐cytoskeleton pathway in adult spinal muscular atrophy patients

Siranosian

Nery

Alves

et al. 2020

Ann Clin Transl Neurol

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Objective: Recent advances in therapeutics have improved prognosis for severely affected spinal muscular atrophy (SMA) type 1 and 2 patients, while the best method of treatment for SMA type 3 patients with later onset of disease is unknown. To better characterize the SMA type 3 population and provide potential therapeutic targets, we aimed to understand gene expression differences in whole blood of SMA type 3 patients (n = 31) and age-and gendermatched controls (n = 34). Methods: We performed the first large-scale whole blood transcriptomic screen with L1000, a rapid, high-throughput gene expression profiling technology that uses 978 landmark genes to capture a representation of the transcriptome and predict expression of 9196 additional genes. Results: The primary downregulated KEGG pathway in adult SMA type 3 patients was "Regulation of Actin Cytoskeleton," and downregulated expression of key genes in this pathway, including ROCK1, RHOA, and ACTB, was confirmed in the same whole blood samples using RT-qPCR. SMA type 3 patientderived fibroblasts had lower expression of these genes compared to control fibroblasts from unaffected first-degree relatives. Overexpression of SMN levels using an AAV vector in fibroblasts did not normalize ROCK1, RHOA, and ACTB mRNA expression, indicating the involvement of additional genes in cytoskeleton dynamic regulation. Interpretation: Our findings from whole blood and patient-derived fibroblasts suggest SMA type 3 patients have decreased expression of actin cytoskeleton regulators. These observations provide new insights and potential therapeutic targets for SMA patients with longstanding denervation and secondary musculoskeletal pathophysiology.

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RhoA regulates Activin B-induced stress fiber formation and migration of bone marrow-derived mesenchymal stromal cell through distinct signaling

Cited by 10 publications

References 32 publications

mDia1 and Cdc42 Regulate Activin B-Induced Migration of Bone Marrow-Derived Mesenchymal Stromal Cells

mDia1 and Cdc42 Regulate Activin B-Induced Migration of Bone Marrow-Derived Mesenchymal Stromal Cells

Sensory nerve‐deficient microenvironment impairs tooth homeostasis by inducing apoptosis of dental pulp stem cells

Whole‐blood dysregulation of actin‐cytoskeleton pathway in adult spinal muscular atrophy patients

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