Myocardial induction of nucleostemin in response to postnatal growth and pathological challenge

Circ Res. 2008 Jul 3;103(1):89-97. doi: 10.1161/CIRCRESAHA.107.169334. Epub 2008 Jun 2.

Abstract

Stem cell-specific proteins and regulatory pathways that determine self-renewal and differentiation have become of fundamental importance in understanding regenerative and reparative processes in the myocardium. One such regulatory protein, named nucleostemin, has been studied in the context of stem cells and several cancer cell lines, where expression is associated with proliferation and maintenance of a primitive cellular phenotype. We find nucleostemin is present in young myocardium and is also induced following cardiomyopathic injury. Nucleostemin expression in cardiomyocytes is induced by fibroblast growth factor-2 and accumulates in response to Pim-1 kinase activity. Cardiac stem cells also express nucleostemin that is diminished in response to commitment to a differentiated phenotype. Overexpression of nucleostemin in cultured cardiac stem cells increases proliferation while preserving telomere length, providing a mechanistic basis for potential actions of nucleostemin in promotion of cell survival and proliferation as seen in other cell types.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cardiomyopathies / genetics
  • Cardiomyopathies / metabolism*
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / genetics
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Fibroblast Growth Factor 2 / pharmacology
  • GTP-Binding Proteins
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / genetics
  • Heart / growth & development
  • Humans
  • Mice
  • Myocardium / metabolism*
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics
  • Proto-Oncogene Proteins c-pim-1 / genetics
  • Proto-Oncogene Proteins c-pim-1 / metabolism
  • RNA-Binding Proteins
  • Rats
  • Stem Cells / metabolism*

Substances

  • Carrier Proteins
  • GNL3 protein, human
  • Gnl3 protein, rat
  • Nuclear Proteins
  • RNA-Binding Proteins
  • nucleostemin protein, mouse
  • Fibroblast Growth Factor 2
  • PIM1 protein, human
  • Pim1 protein, mouse
  • Pim1 protein, rat
  • Proto-Oncogene Proteins c-pim-1
  • GTP-Binding Proteins