Abi3bp is a multifunctional autocrine/paracrine factor that regulates mesenchymal stem cell biology.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Hodgkinson, CP; Naidoo, V; Patti, KG; Gomez, JA; Schmeckpeper, J; Zhang, Z; Davis, B; Pratt, RE; Mirotsou, M; Dzau, VJ

Published Date

  • August 2013

Published In

Volume / Issue

  • 31 / 8

Start / End Page

  • 1669 - 1682

PubMed ID

  • 23666637

Electronic International Standard Serial Number (EISSN)

  • 1549-4918

International Standard Serial Number (ISSN)

  • 1066-5099

Digital Object Identifier (DOI)

  • 10.1002/stem.1416

Language

  • eng