CONTINUOUS ACTIVATION OF GP130, A SIGNAL-TRANSDUCING RECEPTOR COMPONENT FOR INTERLEUKIN 6-RELATED CYTOKINES, CAUSES MYOCARDIAL HYPERTROPHY IN MICE
CONTINUOUS ACTIVATION OF GP130, A SIGNAL-TRANSDUCING RECEPTOR COMPONENT FOR INTERLEUKIN 6-RELATED CYTOKINES, CAUSES MYOCARDIAL HYPERTROPHY IN MICE
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DOI：
10.1073/pnas.92.11.4862
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发表时间：
1995-05-23
影响因子：
11.1
通讯作者：
TAGA, T
中科院分区：
文献类型：
--
作者：
HIROTA, H;YOSHIDA, K;TAGA, T
为了详细研究gp 130的生理作用并确定gp 130异常激活的病理后果，建立了具有持续激活的gp 130的转基因小鼠。这是通过使来自白细胞介素6（IL-6）和IL-6受体（IL-6 R）转基因系的小鼠交配来进行的。过表达IL-6和IL-6 R的后代表现出gp 130和下游信号分子，急性期反应因子/信号转导子和转录激活子3的组成性酪氨酸磷酸化。令人惊讶的是，这种后代的显着特征是心室心肌肥大和随后增厚的心室壁的心脏，其中gp 130也表达，在成年期。单独过表达IL-6或IL-6 R的转基因小鼠没有表现出可检测到的心肌异常。来自正常小鼠的新生心肌细胞在体外培养时，对IL-6和可溶性形式的IG-6 R的组合作出反应而增大。结果表明，gp 130信号通路的激活导致心肌肥厚，这些信号可能参与心肌的生理调节。
To investigate the physiological roles of gp130 in detail and to determine the pathological consequence of abnormal activation of gp130, transgenic mice having continuously activated gp130 were created. This was carried out by mating mice from interleukin 6 (IL-6) and IL-6 receptor (IL-6R) transgenic lines. Offspring overexpressing both IL-6 and IL-6R showed constitutive tyrosine phosphorylation of gp130 and a downstream signaling molecule, acute phase response factor/signal transducer and activator of transcription 3. Surprisingly, the distinguishing feature of such offspring was hypertrophy of ventricular myocardium and consequent thickened ventricular walls of the heart, where gp130 is also expressed, in adulthood. Transgenic mice overexpressing either IL-6 or IL-6R alone did not show detectable myocardial abnormalities, Neonatal heart muscle cells from normal mice, when cultured in vitro, enlarged in response to a combination of IL-6 and a soluble form of IG-6R. The results suggest that activation of the gp130 signaling pathways leads to cardiac hypertrophy and that these signals might be involved in physiological regulation of myocardium.