Abi3bp Is a Multifunctional Autocrine/Paracrine Factor that Regulates Mesenchymal Stem Cell Biology1. (23rd August 2013)

• Record Type: Journal Article
• 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.
• Is Part Of: Stem cells. Volume 31:Number 8(2013:Aug.)
• Page Start: 1669
• Page End: 1682
• Publication Date: 2013-08-23
• Subjects: Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.1416
• Languages: English
• ISSNs: 1066-5099

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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<sc>TEM</sc> C<sc>ells</sc><italic>2013;31:1669–1682</italic></p> </abstract>