Overexpression of insulin-like growth factor-1 in the heart is coupled with myocyte proliferation in transgenic mice
Overexpression of insulin-like growth factor-1 in the heart is coupled with myocyte proliferation in transgenic mice
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DOI：
10.1073/pnas.93.16.8630
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发表时间：
1996-08-06
影响因子：
11.1
通讯作者：
Anversa, P
中科院分区：
文献类型：
--
作者：
Reiss, K;Cheng, W;Anversa, P
产生转基因小鼠，其中人胰岛素样生长因子1B（IGF-1B）的cDNA置于大鼠α-肌球蛋白重链启动子的控制下。在转基因杂合子小鼠中，IGF-1B mRNA在妊娠结束时胎儿心脏中检测不到，出生后1天处于中等水平，并随着出生后成熟而逐渐增加，在75天时达到峰值。从转基因小鼠中分离的肌细胞每24小时每10（6）个细胞分泌1.15 +/- 0.25 ng IGF-1，而纯合野生型同窝小鼠的肌细胞为0.27 +/- 0.10 ng。转基因小鼠血浆IGF-1水平升高84%。在45日龄内，野生型同窝小鼠和转基因小鼠的心脏重量相当，但在出生后75、135、210和380天分别增加了42%、45%、62%和51%。在45、75和210天，心脏中的肌细胞数量分别增加了21%、31%和55%。在转基因动物中。相比之下，在所有年龄的转基因小鼠和中枢小鼠中，肌细胞体积相当。总之，心肌细胞中IGF-1的过度表达导致心脏肥大，这是由心脏中细胞数量增加介导的。
Transgenic mice were generated in which the cDNA for the human insulin-like growth factor 1B (IGF-1B) was placed under the control of a rat alpha-myosin heavy chain promoter. In mice heterozygous for the transgene, IGF-1B mRNA was not detectable in the fetal heart at the end of gestation, was present in modest levels at 1 day after birth, and increased progressively with postnatal maturation, reaching a peak at 75 days. Myocytes isolated from trans,oenic mice secreted 1.15 +/- 0.25 ng of IGF-1 per 10(6) cells per 24 hr versus 0.27 +/- 0.10 ng in myocytes from homozygous wild-type littermates. The plasma level of IGF-1 increased 84% in transgenic mice. Heart weight mas comparable in wild-type littermates and transgenic mice up to 45 days of age, but a 42%, 45%, 62%, and 51% increase was found at 75, 135, 210, anal 380 days, respectively, after birth, At 45, 75, and 210 days, the number of myocytes in the heart was 21%, 31%, and 55% higher, respectively, in transgenic animals. In contrast, myocyte cell volume was comparable in transgenic and central mice at all ages. In conclusion, overexpression of IGF-1 in myocytes leads to cardiomegaly mediated by an increased number of cells in the heart.