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p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes.

Publication ,  Journal Article
Engel, FB; Schebesta, M; Duong, MT; Lu, G; Ren, S; Madwed, JB; Jiang, H; Wang, Y; Keating, MT
Published in: Genes Dev
May 15, 2005

Adult mammalian cardiomyocytes are considered terminally differentiated and incapable of proliferation. Consequently, acutely injured mammalian hearts do not regenerate, they scar. Here, we show that adult mammalian cardiomyocytes can divide. One important mechanism used by mammalian cardiomyocytes to control cell cycle is p38 MAP kinase activity. p38 regulates expression of genes required for mitosis in cardiomyocytes, including cyclin A and cyclin B. p38 activity is inversely correlated with cardiac growth during development, and its overexpression blocks fetal cardiomyocyte proliferation. Activation of p38 in vivo by MKK3bE reduces BrdU incorporation in fetal cardiomyocytes by 17.6%. In contrast, cardiac-specific p38alpha knockout mice show a 92.3% increase in neonatal cardiomyocyte mitoses. Furthermore, inhibition of p38 in adult cardiomyocytes promotes cytokinesis. Finally, mitosis in adult cardiomyocytes is associated with transient dedifferentiation of the contractile apparatus. Our findings establish p38 as a key negative regulator of cardiomyocyte proliferation and indicate that adult cardiomyocytes can divide.

Duke Scholars

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Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

May 15, 2005

Volume

19

Issue

10

Start / End Page

1175 / 1187

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Rats, Wistar
  • Rats
  • Oligonucleotide Array Sequence Analysis
  • Myocytes, Cardiac
  • Mitosis
  • Mice, Knockout
  • Mice
  • MAP Kinase Signaling System
  • Gene Expression Regulation
 

Citation

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Engel, F. B., Schebesta, M., Duong, M. T., Lu, G., Ren, S., Madwed, J. B., … Keating, M. T. (2005). p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev, 19(10), 1175–1187. https://doi.org/10.1101/gad.1306705
Engel, Felix B., Michael Schebesta, Mychelle T. Duong, Gang Lu, Shuxun Ren, Jeffery B. Madwed, Huiping Jiang, Yibin Wang, and Mark T. Keating. “p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes.Genes Dev 19, no. 10 (May 15, 2005): 1175–87. https://doi.org/10.1101/gad.1306705.
Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, et al. p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev. 2005 May 15;19(10):1175–87.
Engel, Felix B., et al. “p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes.Genes Dev, vol. 19, no. 10, May 2005, pp. 1175–87. Pubmed, doi:10.1101/gad.1306705.
Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, Jiang H, Wang Y, Keating MT. p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev. 2005 May 15;19(10):1175–1187.

Published In

Genes Dev

DOI

ISSN

0890-9369

Publication Date

May 15, 2005

Volume

19

Issue

10

Start / End Page

1175 / 1187

Location

United States

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Rats, Wistar
  • Rats
  • Oligonucleotide Array Sequence Analysis
  • Myocytes, Cardiac
  • Mitosis
  • Mice, Knockout
  • Mice
  • MAP Kinase Signaling System
  • Gene Expression Regulation