TY - JOUR
T1 - Leukemia inhibitory factor, a potent cardiac hypertrophic cytokine, activates the JAK/STAT pathway in rat cardiomyocytes
AU - Kodama, Hiroaki
AU - Fukuda, Keiichi
AU - Pan, Jing
AU - Makino, Shinji
AU - Baba, Akiyasu
AU - Hori, Shingo
AU - Ogawa, Satoshi
PY - 1997
Y1 - 1997
N2 - Leukemia inhibitory factor (LIF) is a member of the interleukin-6 family of cytokines, which induces a wide range of responses in a variety of cells. The aim of this study was to investigate whether LIF induces cardiomyocyte hypertrophy and transmits signals through the JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) pathway in primary cultured neonatal rat cardiomyocytes. LIF increased protein content and [3H]phenylalanine uptake in cardiomyocytes in a dose-dependent manner. LIF (103 U/mL) induced rapid tyrosine phosphorylation of gp130, JAK1, JAK2, STAT1, and STAT3 but not Tyk2 or STAT2. LIF also induced autokinase activity of JAK1 in a time-dependent manner. Gel shift assays for interferon gamma activation site/interferon-stimulated responsive element and sis-inducible element (SIE) revealed that LIF induced dimerization of STAT1 and STAT3 and formation of sis-inducing factor complexes, which subsequently interacted with SIE in the promoter. Preincubation with anti-STAT1 and anti-STAT3 antibodies inhibited the binding of SIF complexes. In conclusion, LIF induces cardiac hypertrophy and directly stimulates the JAK/STAT pathway in cardiomyocytes.
AB - Leukemia inhibitory factor (LIF) is a member of the interleukin-6 family of cytokines, which induces a wide range of responses in a variety of cells. The aim of this study was to investigate whether LIF induces cardiomyocyte hypertrophy and transmits signals through the JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) pathway in primary cultured neonatal rat cardiomyocytes. LIF increased protein content and [3H]phenylalanine uptake in cardiomyocytes in a dose-dependent manner. LIF (103 U/mL) induced rapid tyrosine phosphorylation of gp130, JAK1, JAK2, STAT1, and STAT3 but not Tyk2 or STAT2. LIF also induced autokinase activity of JAK1 in a time-dependent manner. Gel shift assays for interferon gamma activation site/interferon-stimulated responsive element and sis-inducible element (SIE) revealed that LIF induced dimerization of STAT1 and STAT3 and formation of sis-inducing factor complexes, which subsequently interacted with SIE in the promoter. Preincubation with anti-STAT1 and anti-STAT3 antibodies inhibited the binding of SIF complexes. In conclusion, LIF induces cardiac hypertrophy and directly stimulates the JAK/STAT pathway in cardiomyocytes.
KW - Cardiac hypertrophy
KW - JAK kinase
KW - Leukemia inhibitory factor
KW - Signal transducer(s) and activator(s) of transcription
KW - Signal transduction
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U2 - 10.1161/01.RES.81.5.656
DO - 10.1161/01.RES.81.5.656
M3 - Article
C2 - 9351438
AN - SCOPUS:0030696081
SN - 0009-7330
VL - 81
SP - 656
EP - 663
JO - Circulation Research
JF - Circulation Research
IS - 5
ER -