ArticleStem cell research & therapy2015
ROCK activity and the Gβγ complex mediate chemotactic migration of mouse bone marrow-derived stromal cells.
Article in Stem cell research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 13 citations in OpenAlex.
- Review
- Sustainably cultured coral scaffold supports human bone marrow mesenchymal stromal cell osteogenesis.Regenerative therapy · 2024Article
- Cyasterone accelerates fracture healing by promoting MSCs migration and osteogenesis.Journal of orthopaedic translation · 2021Article
- Dissecting molecular mechanisms underlying HStem cell research & therapy · 2020Article
- PTH(1‑34) activates the migration and adhesion of BMSCs through the rictor/mTORC2 pathway.International journal of molecular medicine · 2020Article
- SAK-HV Promotes RAW264.7 cells Migration Mediated by MCP-1 via JNK and NF-κB Pathways.International journal of biological sciences · 2018Article
- The G Protein-Coupled Receptor UT of the Neuropeptide Urotensin II Displays Structural and Functional Chemokine Features.Frontiers in endocrinology · 2017Review
- Human umbilical cord mesenchymal stem cells delivering sTRAIL home to lung cancer mediated by MCP-1/CCR2 axis and exhibit antitumor effects.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
introductionBone marrow-derived stromal cells (BMSCs), also known as mesenchymal stem cells, are the focus of intensive efforts worldwide to elucidate their function and biology. Despite the importance of BMSC migration for their potential therapeutic uses, the mechanisms and signalling governing stem cell migration are still not fully elucidated.
methodsWe investigated and detailed the effects of MCP-1 activation on BMSCs by using inhibitors of G protein-coupled receptor alpha beta (GPCR αβ), ROCK (Rho-associated, coiled-coil containing protein kinase), and PI3 kinase (PI3K). The effects of MCP-1 stimulation on intracellular signalling cascades were characterised by using immunoblotting and immunofluorescence. The effectors of MCP-1-mediated migration were investigated by using migration assays (both two-dimensional and three-dimensional) in combination with inhibitors.
resultsWe established the kinetics of the MCP-1-activated signalling cascade and show that this cascade correlates with cell surface re-localisation of chemokine (C motif) receptor 2 (CCR2) (the MCP-1 receptor) to the cell periphery following MCP-1 stimulation. We show that MCP-1-initiated signalling is dependent on the activation of βγ subunits from the GPCR αβγ complex. In addition, we characterise a novel role for PI3Kγ signalling for the activation of both PAK and ERK following MCP-1 stimulation. We present evidence that the Gβγ complex is responsible for PI3K/Akt, PAK, and ERK signalling induced by MCP-1 in BMSCs. Importantly, we found that, in BMSCs, inhibition of ROCK significantly inhibits MCP-1-induced chemotactic migration, in contrast to previous reports in other systems.
conclusionsOur results indicate differential chemotactic signalling in mouse BMSCs, which has important implications for the translation of in vivo mouse model findings into human trials. We identified novel components and interactions activated by MCP-1-mediated signalling, which are important for stem cell migration. This work has identified additional potential therapeutic targets that could be manipulated to improve BMSC delivery and homing.
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