title: Wnt5a increases cardiac gene expressions of cultured human circulating progenitor cells via a PKC delta activation.
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.
  
  
  RESULTS
  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
  These data indicate that Wnt5a enhances cardiac gene expressions of EPC via an activation of PKC delta.
authors.affiliation: Institute of Cardiovascular Regeneration, Center for Molecular Medicine, JW Goethe University, Frankfurt, Germany.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Koyanagi
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Judith
authors.initials: J
authors.lastname: Haendeler
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Zeiher
authors.forename: Stefanie
authors.initials: S
authors.lastname: Dimmeler
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D018920:Coculture Techniques; D004789:Enzyme Activation; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D051745:Protein Kinase C-delta / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology*; D051153:Wnt Proteins / Q000096:biosynthesis* / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051745:Protein Kinase C-delta