Wnt5a increases cardiac gene expressions of cultured human circulating progenitor cells via a PKC delta activation
- 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.
Author: | Masamichi Koyanagi, Masayoshi Iwasaki, Judith HaendelerORCiDGND, Michael Leitges, Andreas M. ZeiherORCiDGND, Stefanie DimmelerORCiDGND |
---|---|
URN: | urn:nbn:de:hebis:30-73723 |
DOI: | https://doi.org/10.1371/journal.pone.0005765 |
ISSN: | 1932-6203 |
Parent Title (English): | PLoS One |
Document Type: | Article |
Language: | English |
Date of Publication (online): | 2009/06/02 |
Date of first Publication: | 2009/06/02 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2010/01/21 |
Volume: | 4 |
Issue: | (6): e5765 |
Note: | 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. |
Source: | PLoS ONE 4(6): e5765. doi:10.1371/journal.pone.0005765 |
HeBIS-PPN: | 222812508 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Licence (German): | Creative Commons - Namensnennung 3.0 |