TY  - JOUR
A1  - Koyanagi, Masamichi
A1  - Iwasaki, Masayoshi
A1  - Haendeler, Judith
A1  - Leitges, Michael
A1  - Zeiher, Andreas M.
A1  - Dimmeler, Stefanie
T1  - Wnt5a increases cardiac gene expressions of cultured human circulating progenitor cells via a PKC delta activation
T2  - PLoS One
N2  - 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 Ca2+-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 Ca2+-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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/7448
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-73723
SN  - 1932-6203
N1  - Copyright:  2009 Koyanagi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 4
IS  - (6): e5765
ER  -