Open AccessAbi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology
Author(s) -
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.
Publication year - 2013
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.1416
Subject(s) - biology , mesenchymal stem cell , microbiology and biotechnology , paracrine signalling , gene knockdown , stem cell , conditional gene knockout , autocrine signalling , paxillin , focal adhesion , protein kinase b , cancer research , signal transduction , cell culture , receptor , biochemistry , genetics , gene , phenotype
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. S TEM C ells 2013;31:1669–1682