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ROCK activity and the Gβγ complex mediate chemotactic migration of mouse bone marrow-derived stromal cells

Overview of attention for article published in Stem Cell Research & Therapy, July 2015
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3 tweeters

Citations

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11 Dimensions

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18 Mendeley

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Title
ROCK activity and the Gβγ complex mediate chemotactic migration of mouse bone marrow-derived stromal cells
Published in
Stem Cell Research & Therapy, July 2015
DOI 10.1186/s13287-015-0125-y
Pubmed ID
26204937
Authors

Caroline M. Ryan, James A. L. Brown, Emer Bourke, Áine M. Prendergast, Claire Kavanagh, Zhonglin Liu, Peter Owens, Georgina Shaw, Walter Kolch, Timothy O’Brien, Frank P. Barry

Abstract

Bone 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. We investigated and detailed the effects of MCP-1 activation on BMSC using inhibitors of GPCR αβ, ROCK and PI3K. The effects of MCP-1 stimulation on intracellular signalling cascades were characterised using immunoblotting and immunofluorescence. The effectors of MCP-1 mediated migration were investigated using migration assays (both 2D and 3D), in combination with inhibitors. We established the kinetics of the MCP-1 activated signalling cascade and show this cascade correlates with cell surface re-localisation of 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 characterize 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 signaling induced by MCP-1 in BMSCs. Importantly, we found that in BMSC inhibition of ROCK significantly inhibits MCP-1 induced chemotactic migration, in contrast to previous reports in other systems. Our results indicate differential chemotactic signalling in mouse BMSC, 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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Twitter Demographics

The data shown below were collected from the profiles of 3 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 18 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 18 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 4 22%
Student > Master 3 17%
Researcher 2 11%
Student > Ph. D. Student 2 11%
Professor 1 6%
Other 2 11%
Unknown 4 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 7 39%
Medicine and Dentistry 2 11%
Agricultural and Biological Sciences 2 11%
Immunology and Microbiology 1 6%
Psychology 1 6%
Other 3 17%
Unknown 2 11%

Attention Score in Context

This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 January 2018.
All research outputs
#7,443,813
of 12,347,188 outputs
Outputs from Stem Cell Research & Therapy
#555
of 1,038 outputs
Outputs of similar age
#116,774
of 237,608 outputs
Outputs of similar age from Stem Cell Research & Therapy
#19
of 44 outputs
Altmetric has tracked 12,347,188 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,038 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.3. This one is in the 41st percentile – i.e., 41% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 237,608 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 46th percentile – i.e., 46% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 44 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 50% of its contemporaries.

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