| First Author | Koyanagi M | Year | 2009 |
| Journal | PLoS One | Volume | 4 |
| Issue | 6 | Pages | e5765 |
| PubMed ID | 19492056 | Mgi Jnum | J:161586 |
| Mgi Id | MGI:4459817 | Doi | 10.1371/journal.pone.0005765 |
| Citation | Koyanagi M, et al. (2009) Wnt5a increases cardiac gene expressions of cultured human circulating progenitor cells via a PKC delta activation. PLoS One 4(6):e5765 |
| abstractText | BACKGROUND: Wnt signaling controls the balance between stem cell proliferation and differentiation and body patterning throughout development. Previous data demonstrated that non-canonical Wnts (Wnt5a, Wnt11) increased cardiac gene expression of circulating endothelial progenitor cells (EPC) and bone marrow-derived stem cells cultured in vitro. Since previous studies suggested a contribution of the protein kinase C (PKC) family to the Wnt5a-induced signalling, we investigated which PKC isoforms are activated by non-canonical Wnt5a in human EPC. METHODOLOGY/PRINCIPAL FINDINGS: Immunoblot experiments demonstrated that Wnt5a selectively activated the novel PKC isoform, PKC delta, as evidenced by phosphorylation and translocation. In contrast, the classical Ca(2+)-dependent PKC isoforms, PKC alpha and beta2, and one of the other novel PKC isoforms, PKC epsilon, were not activated by Wnt5a. The PKC delta inhibitor rottlerin significantly blocked co-culture-induced cardiac differentiation in vitro, whereas inhibitors directed against the classical Ca(2+)-dependent PKC isoforms or a PKC epsilon-inhibitory peptide did not block cardiac differentiation. In accordance, EPC derived from PKC delta heterozygous mice exhibited a significant reduction of Wnt5a-induced cardiac gene expression compared to wild type mice derived EPC. CONCLUSIONS/SIGNIFICANCE: These data indicate that Wnt5a enhances cardiac gene expressions of EPC via an activation of PKC delta. |
