TGFβ inducible early gene-1 (TIEG1) and cardiac hypertrophy:: Discovery and characterization of a novel signaling pathway
TGFβ inducible early gene-1 (TIEG1) and cardiac hypertrophy:: Discovery and characterization of a novel signaling pathway
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DOI：
10.1002/jcb.21049
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发表时间：
2007-02-01
影响因子：
4
通讯作者：
Spelsberg, Thomas C.
中科院分区：
文献类型：
--
作者：
Rajamannan, Nalini M.;Subramaniam, Malayannan;Spelsberg, Thomas C.
引起心脏肥大的细胞机制目前正在深入研究中。我们报告了一个新的发现，在TGF β诱导早期基因（TIEG）空小鼠牵连TIEG 1在心脏肥大。研究了TIEG（-/-）敲除小鼠。使用超声心动图、通过基因微阵列的转录谱分析和免疫组织化学定位上调基因以确定细胞机制来表征4-16个月龄的雄性小鼠（总共N = 86）。雌性小鼠（N = 40）未发生肥大或纤维化。TIEG（-/-）基因敲除小鼠出现了心脏肥大的特征，包括不对称性室间隔肥大，16月龄时心室大小增加，小鼠心脏/体重体重比TIEG（-/-）增加（214%），TIEG（-/-）小鼠的室壁厚度增加，（1.85 ± 0.21 mm），与对照组（1.13 ± 0.15 mm，P < 0.04）相比。Masson三色染色显示肌细胞排列紊乱和成纤维细胞纤维化。左心室的微阵列分析表明，TIEG（-/-）心脏组织表达的垂体肿瘤转化基因-1（Pttg 1）增加了13.81倍。在TIEG（-/-）小鼠心脏组织中证实了Pttg 1和组蛋白H3蛋白水平的增加。我们目前的证据表明，TIEG和可能的靶基因，Pttg 1，在TIEG无效小鼠的心脏肥大的发展。
Cellular mechanisms causing cardiac hypertrophy are currently under intense investigation. We report a novel finding in the TGF beta inducible early gene (TIEG) null mouse implicating TIEG1 in cardiac hypertrophy. The TIEG(-/-) knock-out mouse was studied. Male mice age 4-16 months were characterized (N = 86 total) using echocardiography, transcript profiling by gene microarray, and immunohistochemistry localized upregulated genes for determination of cellular mechanism. The female mice (N = 40) did not develop hypertrophy or fibrosis. The TIEG(-/-) knock-out mouse developed features of cardiac hypertrophy including asymmetric septal hypertrophy, an increase in ventricular size at age 16 months, an increase (214%) in mouse heart/weight body weight ratio TIEG(-/-), and an increase in wall thickness in TIEG(-/-) mice of (1.85 +/- 0.21 mm), compared to the control (1.13 +/- 0.15 mm, P < 0.04). Masson Trichrome staining demonstrated evidence of myocyte disarray and rnyofibroblast fibrosis. Microarray analysis of the left ventricles demonstrated that TIEG(-/-) heart tissues expressed a 13.81-fold increase in pituitary turnor-transforming gene-1 (Pttg1). An increase in Pttg1 and histone H3 protein levels were confirmed in the TIEG(-/-) mice hearts tissues. We present evidence implicating TIEG and possibly its target gene, Pttg1, in the development of cardiac hypertrophy in the TIEG null mouse.