Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival.
We have recently isolated a novel cytokine, cardiotrophin-1 (CT-1), from an in vitro embryonic stem cell system of cardiogenesis that can activate embryonic markers in neonatal rat cardiac myocytes. CT-1 is a new member of the interleukin 6 (IL-6)/leukemia inhibitory factor (LIF) cytokines, which activate downstream signals via gp130-dependent pathways. To define the developmental pattern of expression of CT-1 during murine embryogenesis, we have developed antibodies directed against a CT-1 fusion protein. As assessed by immunolocalization, CT-1 is predominantly expressed in the early mouse embryonic heart tube (E8.5-10.5). In the heart, CT-1 is primarily expressed in myocardial cells, and not in endocardial cushion or outflow tract tissues. After E12.5, CT-1 expression is found in other tissues, including skeletal, liver and dorsal root ganglia. Given the effects of a related family member (ciliary neurotrophic factor, CNTF) on neuronal cell survival, we studied the ability of CT-1 to promote cardiac myocyte survival and proliferation in vitro. Both CT-1 and LIF, which share the same receptors, dramatically promote neonatal cardiac myocyte survival, while IL-6 and CNTF are without effect. A cell proliferation assay documents that CT-1 provokes an approximate 2-fold increase in embryonic cardiac myocyte proliferation. Thus, CT-1 may play an autocrine role during cardiac chamber growth and morphogenesis by promoting the survival and proliferation of immature myocytes, most likely via gp130-dependent signaling pathways.
Sheng
Z
Z
Department of Medicine, Center for Molecular Genetics, University of California , San Diego, School of Medicine, La Jolla, 92093-0613, USA.
Pennica
D
D
Wood
W I
WI
Chien
K R
KR
D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002455:Cell Division; D002470:Cell Survival; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000096:biosynthesis*; D017931:DNA Primers; D005314:Embryonic and Fetal Development; D005727:Ganglia, Spinal / Q000196:embryology / Q000378:metabolism; D005786:Gene Expression Regulation; D005865:Gestational Age; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D008099:Liver / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000196:embryology / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009928:Organ Specificity; D016133:Polymerase Chain Reaction; D051381:Rats; D013234:Stem Cells / Q000502:physiology
D016207:Cytokines; D017931:DNA Primers; C092073:cardiotrophin 1