Abstract 15822: Epidermacan: A Novel Stem Cell Derived Paracrine Factor Mediates Angiogenesis via Regulation of MicroRNAs
Introduction: MicroRNAs (miRNA) are small non-coding RNAs, which regulate gene expression and play an important role in cardiac hypertrophy, fibrosis, angiogenesis, and vessel remodeling. Previous work in our laboratory has demonstrated that mesenchymal stem cells genetically modified to overexpress Akt-1 (Akt-MSCs) promote cardiac repair by expressing enhanced levels of paracrine factors such as Sfrp2, Vegf and Igf-1. Here, we identify epidermacan, a novel protein, as secreted by Akt-MSCs and explore the hypothesis that it promotes angiogenesis via regulation of microRNAs.
Methods and Results: Epidermacan is a glycosylated, disulfide-bonded secretory protein that contains fibronectin type III domains. A dramatic up-regulation of epidermacan mRNA in Akt-MSCs compared to control MSCs was revealed in microarray analysis, and was subsequently confirmed by quantitative RT-PCR. Epidermacan protein was present both in secreted form and membrane-associated form in cultured Akt-MSCs. His-tagged epidermacan recombinant protein produced in bacteria was used to study function of epidermacan in vitro. Our data show that epidermacan promotes human umbilical vein endothelial cell attachment, proliferation and tube formation in vitro. Further analysis using miRNA array profiling comparing epidermacan to known angiogenic factors VEGF and FGF revealed they shared a common miRNA signature. This list included known angiogenic miRNAs such as miR132, miR126*, miR424 and miR130a as well as novel miRNAs that were up-regulated by all three treatments.
Conclusion: In conclusion, our data suggest that epidermacan is a novel stem cell derived paracrine factor that is up-regulated by Akt and promotes angiogenesis in vitro. Treatment with epidermacan is associated with an increase in angiogenic miRNA expression similar to the one induced by VEGF and/or FGF treatment. Experiments are currently in progress to identify the key miRNAs modulating the epidermacan angiogenic effects in vitro and in vivo.
- © 2011 by American Heart Association, Inc.