Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts

Sho Haginiwa, Taketaro Sadahiro, Hidenori Kojima, Mari Isomi, Fumiya Tamura, Shota Kurotsu, Hidenori Tani, Naoto Muraoka, Noriko Miyake, Koichi Miyake, Keiichi Fukuda, Masaki Ieda

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2 Citations (Scopus)

Abstract

Cardiovascular disease is a leading cause of death worldwide. Mammalian cardiomyocytes (CMs) proliferate during embryonic development, whereas they largely lose their regenerative capacity after birth. Defined factors expressed in cardiac progenitors or embryonic CMs may activate the cell cycle and induce CM proliferation in postnatal and adult hearts. Here, we report that the overexpression of Tbx6, enriched in the cardiac mesoderm (progenitor cells), induces CM proliferation in postnatal and adult mouse hearts. By screening 24 factors enriched in cardiac progenitors or embryonic CMs, we found that only Tbx6 could induce CM proliferation in primary cultured postnatal rat CMs. Intriguingly, it did not induce the proliferation of cardiac fibroblasts. We next generated a recombinant adeno-associated virus serotype 9 vector encoding Tbx6 (AAV9-Tbx6) for transduction into mouse CMs in vivo. The subcutaneous injection of AAV9-Tbx6 into neonatal mice induced CM proliferation in postnatal and adult mouse hearts. Mechanistically, Tbx6 overexpression upregulated multiple cell cycle activators including Aurkb, Mki67, Ccna1, and Ccnb2 and suppressed the tumor suppressor Rb1. Thus, Tbx6 promotes CM proliferation in postnatal and adult mouse hearts by modifying the expression of cell cycle regulators.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
DOIs
Publication statusPublished - 2019 Jan 1

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Keywords

  • AAV9
  • Cardiomyocyte
  • Cell cycle
  • Regeneration
  • Tbx6

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Haginiwa, S., Sadahiro, T., Kojima, H., Isomi, M., Tamura, F., Kurotsu, S., Tani, H., Muraoka, N., Miyake, N., Miyake, K., Fukuda, K., & Ieda, M. (2019). Tbx6 induces cardiomyocyte proliferation in postnatal and adult mouse hearts. Biochemical and Biophysical Research Communications. https://doi.org/10.1016/j.bbrc.2019.04.087