p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Engel, FB; Schebesta, M; Duong, MT; Lu, G; Ren, S; Madwed, JB; Jiang, H; Wang, Y; Keating, MT

Published Date

  • May 15, 2005

Published In

Volume / Issue

  • 19 / 10

Start / End Page

  • 1175 - 1187

PubMed ID

  • 15870258

Pubmed Central ID

  • PMC1132004

International Standard Serial Number (ISSN)

  • 0890-9369

Digital Object Identifier (DOI)

  • 10.1101/gad.1306705

Language

  • eng

Conference Location

  • United States