c-kit Is Required for Cardiomyocyte Terminal Differentiation

Pressure overload
DOI: 10.1161/circresaha.107.161737 Publication Date: 2008-02-08T02:36:40Z
ABSTRACT
c-kit, the transmembrane tyrosine kinase receptor for stem cell factor, is required melanocyte and mast development, hematopoiesis, differentiation of spermatogonial cells. We show here that in heart, c-kit expressed not only by cardiac cells but also cardiomyocytes, commencing immediately after birth terminating a few days later, coincident with onset cardiomyocyte terminal differentiation. To examine function differentiation, we used compound heterozygous mice carrying W (null) W(v) (dominant negative) mutations c-kit. In vivo, adult W/W(v) cardiomyocytes are phenotypically indistinguishable from their wild-type counterparts. After acute pressure overload reenter cycle proliferate, leading to left ventricular growth; furthermore transgenic cardiomyocyte-restricted overexpression dominant negative mutant, causes cycle. contrast, growth results mainly hypertrophy. Importantly, overload-induced hyperplasia had improved survival. mice, dysfunction resulted an approximately 14-fold decrease (P<0.01) number c-kit(+)/GATA4(+) progenitors. These findings identify novel functions c-kit: promotion regulation
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