Cell Reports (May 2024)

BMP7 promotes cardiomyocyte regeneration in zebrafish and adult mice

  • Chiara Bongiovanni,
  • Hanna Bueno-Levy,
  • Denise Posadas Pena,
  • Irene Del Bono,
  • Carmen Miano,
  • Stefano Boriati,
  • Silvia Da Pra,
  • Francesca Sacchi,
  • Simone Redaelli,
  • Max Bergen,
  • Donatella Romaniello,
  • Francesca Pontis,
  • Riccardo Tassinari,
  • Laura Kellerer,
  • Ilaria Petraroia,
  • Martina Mazzeschi,
  • Mattia Lauriola,
  • Carlo Ventura,
  • Stephan Heermann,
  • Gilbert Weidinger,
  • Eldad Tzahor,
  • Gabriele D’Uva

Journal volume & issue
Vol. 43, no. 5
p. 114162

Abstract

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Summary: Zebrafish have a lifelong cardiac regenerative ability after damage, whereas mammals lose this capacity during early postnatal development. This study investigated whether the declining expression of growth factors during postnatal mammalian development contributes to the decrease of cardiomyocyte regenerative potential. Besides confirming the proliferative ability of neuregulin 1 (NRG1), interleukin (IL)1b, receptor activator of nuclear factor kappa-Β ligand (RANKL), insulin growth factor (IGF)2, and IL6, we identified other potential pro-regenerative factors, with BMP7 exhibiting the most pronounced efficacy. Bmp7 knockdown in neonatal mouse cardiomyocytes and loss-of-function in adult zebrafish during cardiac regeneration reduced cardiomyocyte proliferation, indicating that Bmp7 is crucial in the regenerative stages of mouse and zebrafish hearts. Conversely, bmp7 overexpression in regenerating zebrafish or administration at post-mitotic juvenile and adult mouse stages, in vitro and in vivo following myocardial infarction, enhanced cardiomyocyte cycling. Mechanistically, BMP7 stimulated proliferation through BMPR1A/ACVR1 and ACVR2A/BMPR2 receptors and downstream SMAD5, ERK, and AKT signaling. Overall, BMP7 administration is a promising strategy for heart regeneration.

Keywords