Abi3bp Regulates Cardiac Progenitor Cell Proliferation and Differentiation
Rationale: Cardiac progenitor cells (CPCs) are believed to differentiate into the major cell types of the heart; cardiomyocytes, smooth muscle cells, and endothelial cells. We have recently identified Abi3bp as a protein important for mesenchymal stem cell (MSC) biology. Since CPCs share several characteristics with MSCs we hypothesized that Abi3bp would similarly affect CPC differentiation and proliferation.
Objective: To determine whether Abi3bp regulates CPC proliferation and differentiation.
Methods and Results: In vivo, genetic ablation of the Abi3bp gene inhibited CPC differentiation whereas CPC number and proliferative capacity was increased. This correlated with adverse recovery following myocardial infarction. In vitro, CPCs, either isolated from Abi3bp knockout mice or expressing an Abi3bp shRNA construct, displayed a higher proliferative capacity and, under differentiating conditions, reduced expression of both early and late cardiomyocyte markers. Abi3bp controlled CPC differentiation via integrin-β1, PKCζ, and Akt.
Conclusions: We have identified Abi3bp as a protein important for CPC differentiation and proliferation.
- Received April 18, 2014.
- Revision received October 6, 2014.
- Accepted October 8, 2014.