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Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways.

Publication ,  Journal Article
Schmeckpeper, J; Verma, A; Yin, L; Beigi, F; Zhang, L; Payne, A; Zhang, Z; Pratt, RE; Dzau, VJ; Mirotsou, M
Published in: J Mol Cell Cardiol
August 2015

Wnt signaling has recently emerged as an important regulator of cardiac progenitor cell proliferation and differentiation, but the exact mechanisms by which Wnt signaling modulates these effects are not known. Understanding these mechanisms is essential for advancing our knowledge of cardiac progenitor cell biology and applying this knowledge to enhance cardiac therapy. Here, we explored the effects of Sfrp2, a canonical Wnt inhibitor, in adult cardiac progenitor cell (CPC) differentiation and investigated the molecular mechanisms involved. Our data show that Sfrp2 treatment can promote differentiation of CPCs after ischemia-reperfusion injury. Treatment of CPCs with Sfrp2 inhibited CPC proliferation and primed them for cardiac differentiation. Sfrp2 binding to Wnt6 and inhibition of Wnt6 canonical pathway was essential for the inhibition of CPC proliferation. This inhibition of Wnt6 canonical signaling by Sfrp2 was important for activation of the non-canonical Wnt/Planar Cell Polarity (PCP) pathway through JNK, which in turn induced expression of cardiac transcription factors and CPC differentiation. Taken together, these results demonstrate a novel role of Sfrp2 and Wnt6 in regulating the dynamic process of CPC proliferation and differentiation, as well as providing new insights into the mechanisms of Wnt signaling in cardiac differentiation.

Duke Scholars

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

August 2015

Volume

85

Start / End Page

215 / 225

Location

England

Related Subject Headings

  • Wnt Signaling Pathway
  • Wnt Proteins
  • Up-Regulation
  • Transcriptional Activation
  • Transcription Factors
  • Stem Cells
  • Proto-Oncogene Proteins
  • Myocytes, Cardiac
  • Mice
  • Membrane Proteins
 

Citation

APA
Chicago
ICMJE
MLA
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Schmeckpeper, J., Verma, A., Yin, L., Beigi, F., Zhang, L., Payne, A., … Mirotsou, M. (2015). Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways. J Mol Cell Cardiol, 85, 215–225. https://doi.org/10.1016/j.yjmcc.2015.06.003
Schmeckpeper, Jeffrey, Amanda Verma, Lucy Yin, Farideh Beigi, Lunan Zhang, Alan Payne, Zhiping Zhang, Richard E. Pratt, Victor J. Dzau, and Maria Mirotsou. “Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways.J Mol Cell Cardiol 85 (August 2015): 215–25. https://doi.org/10.1016/j.yjmcc.2015.06.003.
Schmeckpeper J, Verma A, Yin L, Beigi F, Zhang L, Payne A, et al. Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways. J Mol Cell Cardiol. 2015 Aug;85:215–25.
Schmeckpeper, Jeffrey, et al. “Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways.J Mol Cell Cardiol, vol. 85, Aug. 2015, pp. 215–25. Pubmed, doi:10.1016/j.yjmcc.2015.06.003.
Schmeckpeper J, Verma A, Yin L, Beigi F, Zhang L, Payne A, Zhang Z, Pratt RE, Dzau VJ, Mirotsou M. Inhibition of Wnt6 by Sfrp2 regulates adult cardiac progenitor cell differentiation by differential modulation of Wnt pathways. J Mol Cell Cardiol. 2015 Aug;85:215–225.
Journal cover image

Published In

J Mol Cell Cardiol

DOI

EISSN

1095-8584

Publication Date

August 2015

Volume

85

Start / End Page

215 / 225

Location

England

Related Subject Headings

  • Wnt Signaling Pathway
  • Wnt Proteins
  • Up-Regulation
  • Transcriptional Activation
  • Transcription Factors
  • Stem Cells
  • Proto-Oncogene Proteins
  • Myocytes, Cardiac
  • Mice
  • Membrane Proteins