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

Published

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

Pubmed Central 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