Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy.

DOI Web Site 32 Citations
  • D Pennica
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • K L King
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • K J Shaw
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • E Luis
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • J Rullamas
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • S M Luoh
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • W C Darbonne
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • D S Knutzon
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • R Yen
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.
  • K R Chien
    Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080.

Abstract

<jats:p>Heart failure continues to be a leading cause of mortality worldwide. A hallmark of this disease is dilated cardiac hypertrophy, which is accompanied by a reactivation of genes expressed in fetal heart development. Reasoning that fetal or embryonic growth factors may mediate the onset of cardiac hypertrophy, we have coupled expression cloning with an embryonic stem cell-based model of cardiogenesis to isolate a 21.5-kDa protein, cardiotrophin 1, that potently induces cardiac myocyte hypertrophy in vitro. Amino acid similarity data indicate that cardiotrophin 1 is a member of the leukemia inhibitory factor/ciliary neurotrophic factor/oncostatin M/interleukin 6/interleukin 11 family of cytokines. Several members of this family that are known to signal through the transmembrane protein gp130 stimulate cardiac myocyte hypertrophy, like cardiotrophin 1, suggesting that the gp130 signaling pathway may play a role in cardiac hypertrophy. A 1.4-kb cardiotrophin 1 mRNA is expressed in the heart and several other mouse tissues.</jats:p>

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