Wnt5a increases cardiac gene expressions of cultured human circulating progenitor cells via a PKC delta activation

Masamichi Koyanagi, Masayoshi Iwasaki, Judith Haendeler, Michael Leitges, Andreas M. Zeiher, Stefanie Dimmeler

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Abstract

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.

Original languageEnglish
Article numbere5765
JournalPloS one
Volume4
Issue number6
DOIs
Publication statusPublished - Jun 2 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Koyanagi, M., Iwasaki, M., Haendeler, J., Leitges, M., Zeiher, A. M., & Dimmeler, S. (2009). Wnt5a increases cardiac gene expressions of cultured human circulating progenitor cells via a PKC delta activation. PloS one, 4(6), [e5765]. https://doi.org/10.1371/journal.pone.0005765