Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology

Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs over‐expressing AKT1 (Akt‐MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp toward MSC biology...

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Bibliographic Details
Published in:Stem cells (Dayton, Ohio) Ohio), 2013-08, Vol.31 (8), p.1669-1682
Main Authors: Hodgkinson, Conrad P., Naidoo, Vinogran, Patti, Karl G., Gomez, Jose A., Schmeckpeper, Jeffrey, Zhang, Zhiping, Davis, Bryce, Pratt, Richard E., Mirotsou, Maria, Dzau, Victor J.
Format: Article
Language:English
Subjects:
Animals
Autocrine Communication
Bone marrow
Carrier Proteins - metabolism
Carrier Proteins - physiology
Cell Communication - physiology
Cell Differentiation - physiology
Cell Growth Processes - physiology
Cell Movement - physiology
Cell signaling
Extracellular matrix
Integrin
Male
Mesenchymal Stem Cell Transplantation - methods
Mesenchymal stem cells
Mesenchymal Stromal Cells - cytology
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - physiology
Mice
Mice, Inbred C57BL
Mice, Knockout
Paracrine Communication
Proto-Oncogene Proteins c-akt - metabolism
Stem cells
Transfection
Ubiquitin - metabolism
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Summary:Mesenchymal stem cells (MSCs) transplanted into injured myocardium promote repair through paracrine mechanisms. We have previously shown that MSCs over‐expressing AKT1 (Akt‐MSCs) exhibit enhanced properties for cardiac repair. In this study, we investigated the relevance of Abi3bp toward MSC biology. Abi3bp formed extracellular deposits with expression controlled by Akt1 and ubiquitin‐mediated degradation. Abi3bp knockdown/knockout stabilized focal adhesions and promoted stress‐fiber formation. Furthermore, MSCs from Abi3bp knockout mice displayed severe deficiencies in osteogenic and adipogenic differentiation. Knockout or stable knockdown of Abi3bp increased MSC and Akt‐MSC proliferation, promoting S‐phase entry via cyclin‐d1, ERK1/2, and Src. Upon Abi3bp binding to integrin‐β1 Src associated with paxillin which inhibited proliferation. In vivo, Abi3bp knockout increased MSC number and proliferation in bone marrow, lung, and liver. In summary, we have identified a novel extracellular matrix protein necessary for the switch from proliferation to differentiation in MSCs. STEM Cells 2013;31:1669–1682
ISSN:1066-5099
1549-4918
DOI:10.1002/stem.1416